In-House Canine and
Feline Blood Typing
Bernard F. Feldman, DVM, PhD,
VMRCVM
From the Virginia Tech and
University of Maryland,
Virginia-Maryland Regional
College of Veterinary Medicine,
Polytechnic Institute and
State University,
Blacksburg, Virginia 24061-0442.
JOURNAL of the American Animal Hospital Association
Transfusion Reactions
In 1901, Lansteiner1 first described what we now know as red cell blood
groups. Within a few years, canine blood groups were described. As we
approach the 21st millennium, the veterinary profession should change
our century-old approach to transfusion medicine. When we provide
blood products, they should help, not harm, our patients. We learned
“primum non nocere”—first do no harm. Transfusion reactions indicate
that what you have administered is not working, that what you have given
is causing problems, and that you are burdening an already fragile patient.
Transfusion reactions are clinically manifested by a spectrum of findings.
Just a few include fever, pain at catheter sites, and acute or delayed
hemolysis. Crossmatching, blood typing, or both will eliminate most
transfusion reactions. Both tests should be accomplished in tandem.
Crossmatching determines the compatibility of donor and patient blood
and assesses the effect of antibodies either in the donor or patient. Blood
typing indicates whether the primary red cell antigens of donor and
patient are identical. Blood typing is essential when immune sensitization
has potentially occurred, has occurred, potentially will occur in the future,
or, in the case of cats, when naturally occurring antibodies to other blood
types are present. A simple rule in transfusion medicine is to never
administer to a patient an antigen that she/he does not already have.
Blood Group Systems and Antigens (Types)
Eleven different blood group systems with eight types have been identi-
fied in the dog. Three different blood types have been identified in the cat.
The most clinically important types in the dog are dog erythrocyte anti-
gens (DEA) 1.1,1.2, and 7. Of these, DEA 1.1 is considered the most
significant. Naturally occurring antibodies to DEA 1.1 and 1.2 are rare.
Naturally occurring antibodies to DEA 7 occur in 15% of dogs. Cat red
cell types are A, B, and AB (these are unrelated to the human A B O
antigens). All cats with A blood type have naturally occurring anti-B
antibodies measured in relatively low titers. All cats with the B blood type
have naturally occurring anti-A antibodies measured in relatively high
titers. Transfusion of these blood types to an incompatible patient will
result in hemolysis, significant morbidity, and, in cats with blood type B,
potential mortality.
455
456 JOURNAL of the American Animal Hospital Association November/December 1999, Vol. 35

Blood Typing
Canine and feline blood typing may be accomplished by
sending ethylenediaminetettraacetic acid (EDTA) anti-
coagulated cold (but not frozen) blood to commercial
laboratories, by using commercially prepared reagents in
your hospital laboratory, or by using commercially avail-
able blood typing cards. The blood typing cardsa have
the advantage of being relatively inexpensive, quick and
easy to use, and require quite small amounts of blood
(0.4 ml of EDTA blood).b The cards depend upon an
agglutination reaction. For DEA 1.1 and feline type A,
monoclonal antibody to those types are impregnated into
the cards. Type A cats have low titer and relatively short-
lived antibodies to feline type B. Therefore, the manu-
facturer uses a lectin with binding specificity for feline
type B antigen in the card test. The kits come with easy-
to-understand instructions and trouble-shooting guide,
agglutination test cards, necessary reagents including
diluent, positive and negative controls, and pipettes and
stirrers. The feline kit comes with feline blood group
report cards. Both kits supply additional referenced in-
formation.
When the kit is received, reagents must be refriger-
ated (controls must not be frozen; frozen control re-
agents will be hemolyzed). The manufacturer indicates
the canine cards are stable at room temperature for 19
months and can be stored in the refrigerator (this does
not lengthen the period of stability, and the cards must be
returned to room temperature before use). The canine
diluent is stable for one year, and the reagents are stable
for six months at 2˚ to 7˚ Celsius.
The feline cards are stable for one year at –20˚ Cel-
sius. (Note: This is different from the canine cards.) The
diluent and control stability is identical to the dog when
appropriately refrigerated. The expiration date for both
kits represents the date of the shortest-dated component
in the kit.
Recognizing potential problems with the controls, the
manufacturer has reduced the size of the control dispens-
ing bottle and will provide additional control materials
for a small cost to users whose controls have expired
before the cards.
product needs over time (just a few examples include
immune-mediated hemolysis, pure red cell aplasia, hy-
poproteinemia, and hemostatic disorders) must be blood
typed and crossmatched (the latter before transfusion of
any blood product).
Blood typing in cats is critical to prevent transfusion
reactions.4 Feline type B red cells transfused into a type
A cat will cause reaction and minimal survivability of
the transfused cells. Feline type A red cells transfused
into a type B cat will cause immediate and catastrophic
anaphylactic reaction. Type A kittens born to type B
queens will have neonatal isoerythrolysis. Determining
blood groups of the queen and tom prior to breeding,
coupled with appropriate genetic counseling, can mini-
mize neonatal isoerythrolysis and fading kitten syndrome.
It is good science and good medicine to be able to
consistently deliver pretransfusion testing in your prac-
tice. The ease and simplicity of canine and feline blood
typing is a big step in a positive direction.
a
Rapid Vet-H Canine and Feline; dms laboratories, Flemington, NJ
b
The author does not have any financial relationship with the company
producing these kits.
References
1. Landsteiner K. Uber Agglutinationserscheinungen normalen menschlichen
Blutes. Wien Klin Wochenschr 1901;14:1132–4.
2. Vriesendorp HM, Albert E, Templeton JW, et al. Joint report on the
second international workshop on canine immunogenetics. Transplant Proc
1976;8:289–314.
3. Swisher SN, Young LE. The blood grouping systems of dogs. Physiol Rev
1961;41:495–520.
4. Auer L, Bell K. The AB blood group system in cats. Anim Blood Groups
Biochem Genet 1961;12:287.

Rationale for Blood Typing

The purpose of pretransfusion testing is to select, for
each patient, blood components that, when transfused,
will have acceptable survival, will not cause clinically
significant destruction of transfused or patient cells, and
which will help, not harm, the patient. When transfusing
blood products, future needs of the patient must be also
considered. Antibodies to incompatible blood products
may form in five to seven days.2 Antibodies developed
in breeding bitches by such sensitization may result in
neonatal isoerythrolysis in subsequent litters. Dog eryth-
rocyte antigen 1.1 is the most lytic factor in canine
transfusion medicine.3 Patients with anticipated blood
 Nasopharyngeal Diseases in Cats:
A Retrospective Study of 53 Cases
(1991–1998)
The records of 53 cats with nasopharyngeal disease were examined. Of the cats with
nasopharyngeal disease, 49% had lymphosarcoma and 28% had polyps. Clinical signs in these
cats were compared to 24 cats with nasal disease alone. Cats with only nasal disease more
commonly had historical nasal discharge and sneeze, whereas cats with nasopharyngeal
disease more often had stertorous respiration, phonation change, and typically reported less
nasal discharge or sneeze. It is important to include nasopharyngeal disease in the differential
diagnosis for cats with nasal discharge, sneeze, stertor, or phonation change.
J Am Anim Hosp Assoc 1999;35:457–61.

Heidi S. Allen, DVM Introduction

Nasal disease in cats has been well described.1 The most common nasal
John Broussard, DVM,
diseases in cats include lymphosarcoma, bacterial or viral rhinitis,
Diplomate ACVIM
cryptococcosis, and lymphoplasmacytic rhinitis. The clinical signs asso-
Kathleen Noone, VMD, ciated with nasal disease include nasal discharge, sneezing, stertor, open-
Diplomate ACVIM mouth breathing, and epistaxis. Published reports of feline nasopharyngeal
disease are primarily of nasopharyngeal polyps. 2,3 One report from Aus-
tralia described five cats with nasopharyngeal cryptococcosis.4 The study
RS reported here was a retrospective study of 53 cats with nasopharyngeal
disease diagnosed by either nasopharyngeal biopsy alone or by computer-
ized tomography (CT) scan followed with a nasal or nasopharyngeal
biopsy. Findings in these 53 cats were compared to 24 cats with primary
nasal disease and no nasopharyngeal involvement.

Materials and Methods

The pathology records and CT scan logs were searched for nasal and
nasopharyngeal disease in cats. Cats included in the study had nasopha-
ryngeal disease noted by digital palpation, CT scan, or endoscopy. All
cats had a nasopharyngeal or nasal biopsy confirming the disease. One
author (Allen) examined all CT scans identified for the presence of a soft-
tissue mass in the nasopharyngeal area. Information on patient age, breed,
sex, date of diagnosis, history (including previous treatments), clinical
signs, and physical examination findings were taken from the medical
records. The medical records of 24 cats with nasal disease, confirmed by
biopsy, and no nasopharyngeal involvement on CT scan were reviewed to
compare histories and clinical signs.

From the
Department of Medicine,
Bobst Hospital of
The Animal Medical Center,
510 East 62nd Street,
New York, New York 10021.
Results
Fifty-three cats met all criteria to be entered into the study. Of the 53 cats,
26 (49%) had lymphosarcoma, 15 (28%) had inflammatory polyps lo-
cated dorsal to the soft palate, and 12 (23%) had other diseases including
squamous cell carcinoma, adenocarcinoma, lymphoplasmocytic rhinitis/
pharyngitis, rhabdomyosarcoma, spindle cell carcinoma, and melanoma.
The mean age of the cats with lymphosarcoma was 10.7 years (range, five
to 19 years). The mean age of the cats with polyps was three years (range,

JOURNAL of the American Animal Hospital Association 457

458 JOURNAL of the American Animal Hospital Association
Figure 1—Normal nasopharyngeal area in a cat as seen
by endoscopy.
four months to seven years), which is similar to the mean
ages previously reported.2,3,5 No sex predilection was
found, and the high percentage of domestic shorthairs
(80%) is consistent with the population of cats seen at
the Bobst Hospital of the Animal Medical Center, where
this study was performed.
Clinical signs and histories of the 24 cats with only
nasal disease and the 53 cats with nasopharyngeal dis-
ease with or without nasal involvement were compared.
A higher percentage of cats with nasal disease alone had
nasal discharge (79%) and sneeze (62.5%) when com-
pared to cats with nasopharyngeal disease. Of the cats
with nasopharyngeal disease, 47% had nasal discharge
and 36% had sneeze. A higher percentage of cats with
nasopharyngeal disease rather than nasal disease only
had stertor (49% versus 29%), weight loss (9% versus
0%), and phonation change (17% versus 4%). Six (11%)
of the cats with nasopharyngeal disease also had severe
unilateral or bilateral waxy otic discharge (n=5) or an
otic mass (n=1) noted on physical examination com-
pared to none of the cats with only nasal disease. Of the
six cats with otic disease, five had inflammatory polyps
and one had lymphosarcoma. Twenty-three cats with na-
sopharyngeal disease had soft palate digital palpation, and
of those cats, 19 (82%) had a palpable soft palate mass.
Discussion
Nasopharyngeal disease is common in cats with upper
respiratory disease. The most common diseases in cats of
this study were lymphosarcoma (primarily in older ani-
mals) and nasopharyngeal polyps (primarily in young
animals). Other diseases included squamous cell carci-
noma, melanoma, lymphocytic-plasmacytic inflam-
mation, adenocarcinoma, and rhabdomyosarcoma.
November/December 1999, Vol. 35
Published reports of nasopharyngeal disease in cats have
only described nasopharyngeal polyps2,3 and crypto-
coccosis.4 This study showed that although polyps are the
most common nasopharyngeal disease in young cats,
they constitute only 24% of all nasopharyngeal disor-
ders. Although Cryptococcus infections in cats are not
rare in New York City (actual incidence is unknown),
the authors did not find the organism in any of the
biopsies submitted for histopathological examination.
Most cats with nasal cryptococcosis infection present
with typical signs of discharge and nasal deformity. Di-
agnosis is usually made from nasal discharge cytology
and serum Cryptococcus antigen levels without the need
for nasopharyngeal imaging.
Clinical signs associated with nasopharyngeal disease
were similar to those associated with other causes of
upper airway disease, including stertor and open-mouth
breathing. Many of the 53 cats with nasopharyngeal
diseases had concurrent nasal involvement, displaying
clinical signs of nasal discharge and sneeze.
Stertor and stridor are often mistaken to be the same
sound. Stridor is a sound that is produced by obstruction
of the laryngeal airway. Dogs with laryngeal paralysis
produce a stridorous sound. Stertor, however, is a sound
produced by a nasal or nasopharyngeal obstruction and
sounds more like a “snore.”
Diagnosis of nasopharyngeal masses can be made by
endoscopy, CT scan, skull radiographs, oral examination
(with or without dental mirrors), digital palpation of the
soft palate [Appendix 1, Figure 9], nasopharyngeal bi-
opsy, or any combination of the above. Biopsy samples
can be taken blindly [Appendix 2, Figure 10] or with
endoscopic guidance. It is important for veterinarians in
private practice to know that a diagnosis can be made
even without access to more sophisticated diagnostic
equipment such as a CT scanner or flexible endo-
scope.
It is recommended that all cats presenting for nasal
disease undergo an oral examination and nasopharyn-
geal palpation. Nasopharyngeal masses are located in the
soft palate region, hard palate region, or both. Soft palate
masses are easy to find by oral examination or soft palate
digital palpation. If a mass is palpated, a biopsy speci-
men should be taken of the nasopharyngeal area in addi-
tion to imaging and biopsy of the nasal cavity [Figures
1–4]. Masses in the hard palate region are not readily
palpated because of the palatine bone but can be imaged
by CT scan, skull radiographs, and flexible endoscopy
[Figures 1, 5–7]. Therefore, if no mass is palpated but
nasopharyngeal disease is suspected due to clinical signs,
an examination of the nasopharyngeal area by CT scan,
skull radiographs, or flexible endoscopy is required. To
only blindly biopsy or flush the nasal cavity without
evaluating the nasopharyngeal area could lead to an in-
accurate or missed diagnosis.
November/December 1999, Vol. 35
Figure 2—Computerized tomography scan of the soft palate
region in a cat without evidence of nasopharyngeal disease.
Arrow points to the nasopharynx.
Figure 3—Computerized tomography scan of a cat with a soft
palate mass. Arrow points to the mass.
Computerized tomography scans are useful in the
diagnostic workup of nasopharyngeal disease. Both bone
and soft tissue window techniques of both the nasal
cavity and the more caudally located nasopharyngeal
area are necessary for proper evaluation [Figure 8].
Masses can be seen dorsal to both the hard and soft
palate regions on CT scans. It is important not to over-
interpret mucous debris as a mass in the nasopharynx.
Masses of the hard palate region are seen on the CT scan
as a mottled mass effect in the ventral and caudal aspect
of the nasopharynx. Those masses associated with nasal
disease may show bony destruction of the palatine bone.
Conclusion
Nasopharyngeal disease is an important cause of feline
upper respiratory signs. Nasopharyngeal disease is fre-
quently associated with concurrent nasal disease but can
exist alone. The nasopharyngeal area should be examined
in all cats with nasal disease, and especially if stertorous
Nasopharyngeal Diseases in Cats 459
Figure 4—Lymphosarcoma of the soft palate in a cat as seen by
endoscopy.
Figure 5—Computerized tomography scan of the hard palate
region in a cat without evidence of nasopharyngeal disease.
Arrow points to the nasopharynx.
respirations or phonation changes are heard. This area can
be examined and biopsied without any specialized or ex-
pensive equipment, and doing so may lead to a more
accurate diagnosis than nasal biopsy alone.
a
Poppin forcep; V. Meuller Allegiance Healthcare Corp., Deerfield, IL
References
1. Bedford PG. Diseases of the nose. In: Ettinger SJ, Feldman EC, eds.
Textbook of veterinary internal medicine. Philadelphia:
WB Saunders, 1995:551–67.
(Continued on next page)
460 JOURNAL of the American Animal Hospital Association November/December 1999, Vol. 35

Figure 8—Midsagittal section of a cat skull. Small triangle shows

the end of the nasal cavity. Large triangle shows the end of the
nasopharyngeal area.
Figure 6—Computerized tomography scan of a cat with a hard
palate mass. Arrow points to the mass. Note minimal involve-
ment of the nasal cavity.

Figure 9—Schematic drawing of digital palpation of the soft

palate in a cat.

Figure 7—Hard palate mass of the cat in Figure 6 as seen by

endoscopy. This cat had minimal involvement of the nasal
cavities as seen on the computerized tomography scan [Figure
6] and could not be palpated with digital examination.

Figure 10—Schematic drawing of a blind biopsy of the nasopha-

References (cont’d) ryngeal area in a cat using poppin forceps.
2. Pope ER. Feline inflammatory polyps. Sem Vet Med Surg 1995;10(2):
87–93.
3. Bradley RL, Noone KE, Saunders GK, et al. Nasopharyngeal and middle
ear polyp masses in five cats. Vet Surg 1985;4:141–4.
4. Malik R, Martin P, Wigney DI, et al. Nasopharyngeal cryptococcosis.
Aust Vet J 1997;75:483–8.
5. Kapatkin AS, Mathiesen DT, Noone KE, et al. Results of surgery and long-
term follow-up in 31 cats with nasopharyngeal polyps.
J Am Anim Hosp Assoc 1990;26:387–92.
November/December 1999, Vol. 35
Appendix 1
Digital Palpation of the Soft Palate
Digital examination of the soft palate can be done in
most cats without sedation. If you are right-handed, use
your left hand to support the cat’s head. Place the index
and fourth finger of your left hand on either side of the
temporomandibular junction, with the palm of your hand
supporting the head. The middle finger of your right
hand is then used to lower the mandible and pry open the
mouth. When the mouth is open, the index finger can slip
in and quicky rotate up to palpate the soft palate [Figure
9]. Practicing on very cooperative cats or sedated cats
will help to perfect your technique.
Nasopharyngeal Diseases in Cats 461
Appendix 2
Blind Biopsy of Nasopharyngeal Masses
Blind biopsies of nasopharyngeal masses are relatively
uncomplicated but need to be done under general anes-
thesia with an endotracheal tube in place. Once the cat is
anesthetized, place it on its back. While keeping the cat’s
head parallel to the table, an assistant should open the
cat’s mouth to its fullest extent. Using a poppin forcep,a
one can reach behind the end of the soft palate, pull it
forward, and biopsy the mass in the nasopharyngeal area
(below the soft palate) [Figure 10].
 Idiopathic Thrombocytopenic
Purpura in a Cat
An 11-year-old, castrated, male domestic shorthair cat was presented for hematuria and
pollakiuria. The cat had a marked thrombocytopenia, and a bone-marrow core biopsy
demonstrated megakaryocytic hyperplasia with many megakaryocyte-associated neutrophils
(i.e., emperipolesis). On peripheral blood, collected at initial presentation, what appeared to be
platelets were noted to be within or adherent to occasional neutrophils. The thrombocytopenia
was idiopathic in that no definitive cause could be found. However, platelet concentrations
appeared to increase and decrease in response to changes in prednisone and cyclosporine
therapy, suggesting a possible immune-mediated pathogenesis. As tests to detect increased
feline platelet-associated antibodies are unavailable, immune-mediated thrombocytopenia can
only be tentatively diagnosed in cats by exclusion and response to therapy.
J Am Anim Hosp Assoc 1999;35:464–70.

Catherine L. Garon, DVM Case Report

Michael A. Scott, DVM, PhD,
Diplomate ACVP
Kim A. Selting, DVM
Leah A. Cohn, DVM, PhD,
Diplomate ACVIM
C range, 1.5 to 7.0 x103/µl) and thrombocytopenia (85 x103/µl; reference
From the Departments of Veterinary
Medicine and Surgery (Garon, Cohn)
and Veterinary Pathobiology (Scott),
University of Missouri
Veterinary Medical Teaching Hospital,
379 East Campus Drive,
Columbia, Missouri 65211
and the Kingsbury Animal Hospital (Selting),
420 North Skinker,
St. Louis, Missouri 63130.
An 11-year-old, castrated, male domestic shorthair cat was presented to
the referring veterinarian for hematuria and pollakiuria. Historically, the
cat had not been allowed outdoors and had no known exposure to toxi-
cants, including rodenticides. Vaccinations were not current (approxi-
mately 10 years past due). Physical examination revealed a bright and
alert cat with petechial hemorrhages on the pinnae and mucous mem-
branes. The cat’s temperature was 101.8˚ F; heart rate was 208 beats per
minute; and respiratory rate was 44 breaths per minute. A complete blood
count (CBC) revealed moderate lymphopenia (0.4 x103/µl; reference
range, 200 to 500 x103/µl). Serum biochemical analysis demonstrated
mild hyperglycemia (219 mg/dl; reference range, 75 to 160 mg/dl). Blood
was negative for feline leukemia virus (FeLV) by enzyme-linked immu-
nosorbent assay (ELISA), feline immunodeficiency virus (FIV) by immu-
nofluorescent antibody assay (IFA), and Haemobartonella felis by IFA.
Serum total thyroxine (TT4) concentration measured by radioimmunoas-
say (RIA) was within the reference range. Ecchymotic hemorrhages were
noted on the ventral abdomen after obtaining urine via cystocentesis. The
urinalysis was consistent with hemorrhage (4+ protein, too numerous to
count [tntc] red blood cells [RBCs] per high-power field [hpf], five to 15
white blood cells [WBCs] per hpf) and transient glucosuria (2,000 mg/dl)
that was probably stress induced.
Several hours after presentation to the referring veterinarian, the packed
cell volume (PCV) and total solids (TS) decreased from 32% to 18%
(reference range, 24% to 45%) and from 6.9 g/dl to 4 g/dl (reference
range, 6 to 8 g/dl), respectively. Activated clotting time (ACT) was
prolonged at greater than 270 seconds. Abdominal ultrasonography re-
vealed a thick urinary bladder and an irregular mass within the bladder.
Treatment consisted of a whole blood transfusion, dexamethasone sodium
phosphate (3 mg/kg body weight, intravenously [IV]), and ampicillin (20
mg/kg body weight, IV once). The cat was referred to the University of
Missouri Veterinary Medical Teaching Hospital (UM-VMTH) the fol-
lowing night.

464 JOURNAL of the American Animal Hospital Association

November/December 1999, Vol. 35
Figure 1—Peripheral blood smear in an 11-year-old domestic
shorthair cat with thrombocytopenia. A platelet or platelet-like
structure is associated with the neutrophil’s cytoplasm. Note the
similarity in staining of the platelet-like structure to the larger
platelet below and to the left of the neutrophil (Hematek stain,
1,900X).
On initial examination at the UM-VMTH (day one),
the cat had petechial hemorrhages on the pinnae and
mucous membranes and ecchymotic hemorrhages on the
ventral abdomen. Thoracic auscultation revealed a grade
II/VI systolic murmur at the left heart apex, rapid and
shallow respirations, and normal lung sounds. The PCV
and TS were 14% and 5.6 g/dl, respectively, but a CBC
was not done. A Coombs’ test was not performed be-
cause of the prior whole blood transfusion and evidence
to support a blood loss anemia. Therapeutics included a
whole blood transfusion, cefoxitin sodiuma (20 mg/kg
body weight, q 6 hr IV), and IV fluids (0.45% NaCl and
2.5% dextrose at a rate of 12 ml per hr). Five hours
posttransfusion, the PCV and TS were 22% and 7.4 g/dl,
respectively.
The following morning (day two), a CBC demon-
strated a low-normal hematocrit (PCV, 25%), mild aniso-
cytosis, moderate lymphopenia (0.5 x103/µl), and marked
thrombocytopenia (less than 1 x103/µl; reference range,
300 to 800 x103/µl). An apparent neutrophil-platelet as-
sociation was noted on the peripheral blood smears. On
each smear, there were several neutrophils that appeared
to contain or have membrane-adherent platelets [Figure
1]. Several other neutrophils contained smaller, pink,
purple, or bluish cytoplasmic inclusions that varied from
homogeneous to granular. These did not have features of
Döhle bodies or Ehrlichia morulae but resembled plate-
lets or platelet fragments. Serum biochemical analysis
revealed mild hypokalemia (3.4 mmol/L; reference range,
Thrombocytopenia in a Cat 465
Figure 2—Bone-marrow core biopsy from the cat in Figure 1.
Several megakaryocytes are present, and two intact neutrophils
appear within megakaryocyte cytoplasm (Hematoxylin and eosin
stain, 900X).
3.5 to 5.1 mmol/L), mild hypoalbuminemia (2.4 g/dl;
reference range, 2.7 to 3.9 g/dl), mild hyperbilirubine-
mia (0.8 mg/dl; reference range, 0.1 to 0.5 mg/dl), and a
two-fold increase in alanine aminotransferase (ALT) (377
U/L; reference range, 20 to 170 U/L). The one-stage
prothrombin time (OSPT) was similar to control (9.5
sec; control, 9.7 sec), and the activated partial thrombo-
plastin time (APTT) was increased at 35.5 sec (control,
15 sec). Blood was submitted for Ehrlichia canis and
Ehrlichia risticii titers, which later proved to be nega-
tive. Serum was not submitted for antinuclear antibody
titers because of the previous whole blood transfusions.
The authors were unable to obtain a voided urine sample.
A bone-marrow aspirate and core biopsy were ob-
tained on day two under general anesthesia (diazepam
[0.5 mg/kg body weight, IV] and ketamine [10 mg/kg
body weight, IV] induction, and maintained on iso-
flurane) for prognostic purposes. The bone-marrow aspi-
rate was very hemodiluted with scattered hematopoietic
cells, including several megakaryocytes. The bone-mar-
row core biopsy was of high-normal cellularity, with
about 75% hematopoietic tissue and only about 25%
adipose tissue. The myeloid:erythroid ratio appeared nor-
mal, with both cell lines appearing moderately hyper-
plastic. There was marked megakaryocytic hyperplasia,
with eight to 20 megakaryocytes per 40-power objective
field. Many of the megakaryocytes had increased nuclear
lobulation with prominent nucleoli, and approximately
25% of them had one to many intracytoplasmic or sur-
face-associated neutrophils [Figure 2].
Radiographs of the thorax demonstrated moderate car-
diomegaly, possible mild pleural effusion, dilatation of
the caudal vena cava, pulmonary edema, and a pro-
nounced pulmonary vascular pattern. Abdominal radio-
graphs were unremarkable, and ultrasonography revealed
466 JOURNAL of the American Animal Hospital Association
Figure 3—Platelet concentrations in an 11-year-old cat
presented with thrombocytopenia; (A) prednisone instituted at 2
mg/kg per os [PO] q 12 hrs; (B) decreased prednisone to 2 mg/
kg PO q 24 hrs; (C) increased prednisone to 2 mg/kg PO q 12
hrs; (D) bone-marrow aspirate and core biopsy; (E) administered
vincristine at 0.025 mg/kg as a single intravenous injection; (F)
cyclosporine instituted at 5 mg/kg PO q 12 hrs; (G) decreased
cyclosporine to 4 mg/kg PO q 12 hrs; (H) decreased cyclosporine
to 2 mg/kg PO q 12 hrs; (I) discontinued prednisone (tapered
over previous two months); (J) decreased cyclosporine to 2 mg/
kg PO q 24 hrs; (K) increased cyclosporine to 2 mg/kg PO q 16
hrs.
• No platelet clumping was found when platelet concentrations
were reported
• Platelet clumping was found on days 65, 86, 97, 121, and 212
• Manual platelet counts: days 2, 3, 4, 5, 6, 7, 105
• Automated platelet count using either a Cell-Dyn or a
Technicon H1 hematology analyzer with slide review: days 1,
20, 29, 40, 129, 153, 182, 236, 294, 301, 317, 351, 365, 372
dorsal thickening of the bladder wall with possible calci-
fication, but no mass was visualized in the bladder. It is
likely that the original mass in the bladder was a he-
matoma.
Additional therapeutics included doxycyclineb (load-
ing dose of 5 mg/kg body weight; maintenance dose of
2.5 mg/kg body weight, per os [PO] q 24 hr) for possible
infectious thrombocytopenia; vitamin K1c (2.5 mg/kg
body weight, subcutaneously [SC] q 12 hr) for a possible
vitamin K deficiency or antagonism despite a normal
OSPT;30 prednisoned (2 mg/kg body weight, PO q 12 hr)
for a possible immune-mediated thrombocytopenia;
furosemidee (1 mg/kg body weight, IV q 12 hr) for
pulmonary edema; and heparin for possible thromboem-
bolic disease (75 U/kg body weight, SC q 8 hr). The
cefoxitin was decreased to q 12 hr, and 20 mEq of
potassium chloride (KCl) was added per liter of 0.45%
NaCl and 2.5% dextrose (infusion rate, 12 ml per hr).
The cat was monitored through the weekend (days three
and four), during which time the respirations remained
shallow and rapid, a gallop rhythm was noted along with
the systolic murmur, and crackles were ausculted in the
lung fields. Marked thrombocytopenia (3 x103/µl on days
three and four), lymphopenia (0.169 x103/µl on day three;
0.240 x103/µl on day four), and neutrophil-platelet asso-
ciation persisted. The PCV and TS remained stable at
24% and 7.2 g/dl, respectively.
November/December 1999, Vol. 35
On day five, thoracic radiographs revealed improve-
ment of the pulmonary edema, and an echocardiogram
revealed hypertrophic cardiomyopathy. The pulmonary
edema was consistent with cardiac decompensation due
to anemia. During the next three days, the cat’s respira-
tory rate returned to normal, and the petechial and ecchy-
motic hemorrhages began to resolve. The anemia
remained relatively stable (PCV, 24% to 28%) and be-
came mildly regenerative, with a PCV-corrected reticu-
locyte percentage of 1.8% (reference range, less than
1.6%) on day seven. The platelet concentration increased
from 74 x103/µl on day five to 238 x103/µl on day seven.
The lymphopenia remained marked (0/µl each day). The
serum biochemical analyses on days five and seven dem-
onstrated mild hypokalemia (2.8 and 3.0 mmol/L, re-
spectively) and a two-fold increase in ALT activity (284
and 277 U/L, respectively). The OSPT (patient, 7.7 sec;
control, 8.5 sec) and APTT (patient, 16.2 sec; control,
14.5 sec) were normal on day seven. The voided urine
had a specific gravity of 1.016 (while on IV fluid
therapy), with two to four granular casts per hpf; no
RBCs were observed.
The cat was discharged seven days after admission
with resolving idiopathic thrombocytopenia and the di-
agnosis of mild to moderate hypertrophic cardiomyopa-
thy (HCM). The HCM was treated with furosemide (1
mg/kg body weight, PO q 24 hr) and atenololf (6.25 mg
PO q 24 hr), and prednisone (2 mg/kg body weight, PO q
12 hr) was continued for possible immune-mediated
thrombocytopenia [Figure 3A]. Doxycycline (2.5 mg/kg
body weight, PO q 24 hr), which had been initiated upon
presentation, was continued for a 10-day regimen. All
other therapies (cefoxitin, vitamin K1, heparin) were dis-
continued. Serum ALT and potassium values were nor-
mal when tested three weeks after discharge. Furosemide
was discontinued one month after discharge.
Over the next 10 months, the cat had multiple recheck
examinations with the referring veterinarian and re-
mained clinically well, despite reports of varying de-
grees of thrombocytopenia. Feline platelets clump easily
during routine blood collection and processing, but plate-
let clumps were not noted on smears corresponding to
any of the reported values. Platelet concentrations ap-
peared to fluctuate in response to changes in doses of
prednisone and cyclosporine [Figure 3]. Two weeks af-
ter discharge from the UM-VMTH, the platelet concen-
tration remained above 200 x103 /µl; therefore, the
prednisone dosing schedule was changed to 2 mg/kg
body weight, q 24 hr [Figure 3B]. Subsequently, lower
values persisted from day 29 (28 x103/µl) to day 40 (97
x103/µl), so prednisone dosing was increased on day 40
to 2 mg/kg body weight, PO q 12 hr [Figure 3C]. A bone-
marrow aspirate and core biopsy were repeated on day
97 because of persistent thrombocytopenia [Figure 3D].
The marrow was moderately cellular, with mild to mod-
erate megakaryocytic hyperplasia (seven to nine
November/December 1999, Vol. 35
megakaryocytes per 40-power objective field) and nor-
mal-appearing leukopoiesis and erythropoiesis. Neutro-
phils were rarely associated with megakaryocytes as they
had been in the initial bone-marrow sample. Because
thrombocytopenia and megakaryocytic hyperplasia were
still present, prednisone was continued at 2 mg/kg body
weight, PO q 12 hr. On day 121, a single IV injection of
vincristine (0.025 mg/kg body weight) was given to in-
crease the circulating platelet numbers [Figure 3E]. There
was minimal improvement in the thrombocytopenia (64
x103/µl) on day 129; therefore, prednisone was contin-
ued and cyclosporine microemulsion (5 mg/kg body
weight, PO q 12 hr) was instituted [Figure 3F]. The
platelet concentration (187 x103/µl) increased dramati-
cally; however, the cat developed gastrointestinal signs
(i.e., vomiting). The cyclosporine was gradually de-
creased (beginning on day 153) to a dose of 2 mg/kg
body weight, PO q 24 hr on day 236 [Figures 3G–3J].
The prednisone was discontinued on day 212 (tapered by
50% monthly over the previous two months). On day
275, the platelet concentration was only 50 x10 3/µl, so
the cyclosporine dose was increased to 2 mg/kg body
weight, PO q 16 hr. The platelet concentration then
remained above 125 x103/µl with no adverse clinical
signs [Figure 3K]. Ten months after initial presentation,
the cat was presented to the referring veterinarian for
melena of one week’s duration. Medications at that time
included cyclosporine (2 mg/kg body weight, PO q 16
hr) and atenolol (6.25 mg PO q 24 hr). Hematological
evaluation revealed a marked regenerative anemia
(PCV, 12%; reticulocytes, 16.2%) with a low-normal
albumin (2.3 g/dl; reference range, 2.1 to 3.9 g/dl)
and globulin (2.3 g/dl; reference range, 1.5 to 5.7
g/dl), consistent with a blood loss anemia. The plate-
let concentration was 175 x10 3/µl; all other values
were normal (including APTT and OSPT). After no
response to conservative treatment (i.e., cimetidine and
sucralfate), upper gastrointestinal endoscopy revealed a
proximal duodenal mass. The mass was surgically re-
moved and diagnosed histopathologically as a gastric
adenoma with clean margins. The cat fully recovered
with no change in platelet concentrations.
Clinical Update
Fifteen months after initial diagnosis, the cat was pre-
sented to the referring veterinarian for vomiting. Physi-
cal examination revealed an abdominal mass. A CBC
revealed platelet clumping. The platelet concentration
subjectively appeared adequate. Surgical removal of the
gastric mass was successful; however, the cat did not
recover postoperatively. Histopathology demonstrated a
marked, focally extensive, chronic pyogranulomatous
inflammation with intralesional, filamentous bacteria
suggestive of Nocardia spp.
Thrombocytopenia in a Cat 467
Discussion
Marked thrombocytopenia is rarely reported in cats. Sig-
nificant thrombocytopenias in cats have been associated
with FeLV, FIV, feline infectious peritonitis (FIP), toxo-
plasmosis, ehrlichiosis, neoplasia, cardiac disease,
thromboboembolism, disseminated intravascular coagu-
lation (DIC), and several drugs including griseofulvin,
doxorubicin, azathioprine, carboplatin, propylthiouracil,
and ribavirin.1–9 In contrast to dogs, immune-mediated
thromobocytopenia has been clinically diagnosed and
reported in only a few cats.10–15 In a retrospective study,
thromocytopenia was observed in only 41 of 3,300 (1.2%)
cats in which CBCs were performed. Only one of the 41
(2%) cases was thought to be due to primary immune-
mediated platelet destruction. 2
Thrombocytopenia in the cat of this report was idio-
pathic in that its cause was not found. The anemia was a
consequence of hemorrhage. The initial presenting signs
of hematuria and petechiae, with a platelet concentration
of 85 x103/µl, suggested platelet dysfunction or a vascu-
lar disorder in addition to thrombocytopenia. A con-
currently prolonged ACT is evidence that the thrombocy-
topenia may have been consumptive, and the presence of
megakaryocytic hyperplasia supports a consumptive or
destructive process. The platelet concentration was ob-
tained several hours prior to the ACT. The concentration
was dropping; therefore, it was possible that the platelet
concentration decreased to a significant level (less than
10 x103 platelets/µl), prolonging the ACT. History, physi-
cal examination, and laboratory data failed to reveal a
cause for prolonged coagulation times such as vasculitis,
and a marked thrombocytopenia persisted in the cat.
The cat was diagnosed with HCM and had signs of
heart failure when it decompensated after becoming ane-
mic secondary to hemorrhage. With severe anemia, sys-
temic vascular resistance falls, decreasing cardiac
afterload and increasing cardiac preload. This results in
cardiac failure due to a high output state or functional
volume overload.16 While thromboembolic disease can
occur secondary to HCM,17,18 thrombocytopenia is rare
and not marked in the absence of overt signs of DIC.2
This cat had no clinical signs typical of thromboembo-
lism, such as cold extremities and limb paresis or paraly-
sis, and no laboratory data to support organ failure or
significant dysfunction. There was no evidence of throm-
bosis on echocardiography or thoracic radiographs. The
right heart size was normal on the echocardiogram, sug-
gesting the lack of pulmonary hypertension. Thoracic
radiographs revealed changes consistent with left heart
failure: pulmonary edema, pulmonary venous distension,
and enlarged left atrium.
There was also no evidence to support other condi-
tions known to be associated with thrombocytopenias or
coagulopathies in cats. There was no known or expected
exposure to any drugs or toxicants, including anticoagu-
468 JOURNAL of the American Animal Hospital Association
lant rodenticides, which have been associated with throm-
bocytopenia in dogs.19 Furthermore, the OSPT (which is
sensitive to vitamin K absence or antagonism) was not
increased. Tests for FeLV, FIV, and ehrlichiosis were
negative. An IFA for FeLV was not performed on slides
of the bone-marrow aspirates because of an insufficient
number of suitable slides. Signs typical of FIP and toxo-
plasmosis were not present and did not develop. Evi-
dence of liver failure, exocrine pancreatic insufficiency
(leading potentially to vitamin K deficiency), and en-
venomation were absent. A gastric adenoma was diag-
nosed 10 months later, but there is little evidence to
suggest a connection to the previous episode of disease.
Hereditary defects of coagulation factors in the intrinsic
pathway (XII, IX, and VIII) were excluded by a normal
APTT 10 months after presentation.
The marked thrombocytopenia and prolonged APTT
resolved rapidly after transfusions, antibiotics, vitamin
K1, immunosuppressive doses of steroids, and heparin.
An immune-mediated component to the platelet destruc-
tion, either primary or secondary to an unidentified pro-
cess, was considered possible because of the initial
response while on prednisone, an apparent relapse of
thrombocytopenia when prednisone was decreased, and
subsequent increases in platelet concentrations after in-
stituting or increasing cyclosporine therapy. It is impor-
tant to note that reported platelet concentrations for
routinely submitted feline samples may be inaccurate
due to the strong tendency of feline platelets to aggregate
after collection. While it is possible that platelet clumps
were present in some of the later samples from the cat in
this report, platelet clumps were looked for and not seen in
every instance where a platelet concentration was reported.
The presence of many megakaryocyte-associated
neutrophils in the initial bone-marrow sample from this
cat was unusual. This finding would generally be
regarded as emperipolesis, which refers to nonphagocytic
engulfment of cells by megakaryocytes without damage
to either the megakaryocyte or the engulfed cell. This
phenomenon has been noted in many humans with
primary immune-mediated thrombocytopenia, but it is
nonspecific, and it has been associated with many other
causes of increased thrombopoiesis.20 There is electron
microscopic evidence that emperipolesis may not always
be benign and that neutrophils may sometimes be
attracted to damaged megakaryocytes.21 Though purely
speculative, it is possible that this cat’s neutrophils were
attracted to antibody-damaged megakaryocytes. Mega-
karyocyte hyperplasia concurrent with impaired throm-
bopoiesis occurs in human patients with immune-mediated
thrombocytopenia.22 Similarly, it is interesting to
speculate about the possible significance of the apparent
neutrophil-associated platelets seen in the peripheral
blood of this cat. A role for neutrophils in the destruction
of antibody-coated canine platelets has been suggested
by in vitro studies, 23 and such a process may have been
November/December 1999, Vol. 35
reflected in this cat’s blood. The presence of antiplatelet
antibodies could also have impaired platelet function,24
which could help explain petechiation when the platelet
concentration was 85 x103/µl.
The increased APTT could have been related to
antiphospholipid antibodies, though they were not as-
sessed. In humans, antiphospholipid antibodies (APA)
are reported to occur in 46% of patients diagnosed with
primary immune-mediated thrombocytopenia, and they
may cause prolongation of the APTT without prolonga-
tion of the OSPT.25,26
Immune-mediated thrombocytopenia can occur alone
or in association with neoplasia, inflammatory disease,
infectious disease, or drug administration. When im-
mune-mediated thrombocytopenia leads to purpura in
the absence of an identifiable cause, it is often referred to
as primary immune-mediated thrombocytopenia. Im-
mune-mediated thrombocytopenia is believed to be
caused by increased antibody (generally immunoglobu-
lin G) binding to platelet membranes, which enhances
destruction of platelets by the mononuclear phagocytic
system.27,28 Immunoglobulins may be directed at auto-
epitopes on the platelet surface, at adsorbed antigens, or
they may be present in the form of adherent immune
complexes. Cells of the mononuclear phagocytic system
(mostly in the spleen) recognize and bind Fc subunits of
platelet-associated immunoglobulin molecules. They
then phagocytize the platelets and process them, together
with any adsorbed antigens, for presentation to adjacent
antibody-producing lymphocytes, thereby amplifying the
immune response.28,29 A healthy bone marrow will re-
spond to platelet destruction by increasing the number
and volume of megakaryocytes. However, antiplatelet
antibodies can cross-react with megakaryocytes and de-
crease thrombopoiesis, thereby exacerbating the
thrombocytopenia despite adequate or increased mega-
karyocytopoiesis.30,31
The diagnosis of primary immune-mediated thrombo-
cytopenia is a tentative diagnosis of exclusion, even in
human medicine where decades of research have re-
sulted in numerous assays for antiplatelet antibodies.32
The most recent assays, antigen capture assays, have
improved specificity for primary immune-mediated
thrombocytopenia, but they still lack clinical utility in
reliably differentiating primary from secondary immune-
mediated thrombocytopenia. Very little work has been
done to develop assays for immune-mediated thrombo-
cytopenia in cats. Several assays have been developed
for dogs, but they are not widely available, they lack
proven specificity for primary immune-mediated throm-
bocytopenia, they have variable sensitivity, and they
have not undergone rigorous clinical testing.27,33
The cat in this case report was treated sequentially
with glucocorticoids, vincristine, and cyclosporine. Glu-
cocorticoids primarily suppress macrophage destruction
of platelets.28 In dogs, vincristine has been shown to
November/December 1999, Vol. 35
increase platelet numbers by causing acute fragmenta- 4.
tion of megakaryocytes and stimulating release of
5.
thrombopoietic factors.34 Cyclosporine indirectly inhib-
its macrophage function and antigen presentation by in-
hibiting T-lymphocyte activation, blocking interleukin-2 6.
transcription, and impairing proliferation of activated T-
helper and T-cytotoxic lymphocytes.35 The cat initially 7.
responded to prednisone but became unresponsive after
the dose was tapered. Vincristine did not elicit a favor-
able response despite an adequate number of megakaryo- 8.
cytes in the bone marrow. However, the authors are
9.
unaware of documentation of the efficacy of vincristine
in thrombocytopenic cats. There was an apparent re- 10.
sponse to cyclosporine at doses of at least 2 mg/kg body
weight, q 16 hr; however, gastrointestinal signs devel-
11.
oped when cyclosporine was administered more
frequently. Because of the variable absorption of 12.
cyclosporine, whole blood levels should have been mea-
sured to assure adequate trough levels.
13.
Conclusion 14.
Thrombocytopenic purpura is uncommon in cats. When
known causes are excluded, primary immune mecha- 15.
nisms should be considered; however, immune-mediated
platelet destruction is difficult to definitively establish. 16.
The cat in this case report had idiopathic thrombocy-
topenic purpura that appeared to begin with a mild, tran-
sient coagulopathy of unknown etiology. Diagnostic and 17.
therapeutic plans were directed at known causes of throm-
bocytopenia in cats, but the cause was not determined in 18.
this case. A contributing immune-mediated pathogenesis
was suggested by the exclusion of other causes, by the
19.
resolution of thrombocytopenia in association with ste-
roid therapy, and by demonstrating repeatable favorable
responses to immunosuppressive therapy. The gastric 20.
adenoma found 10 months after initial presentation ap-
parently played no significant role in the cat’s thrombo- 21.
cytopenia, because its removal was not associated with a
rebound thrombocytosis. The pyogranulomatous gastric
22.
mass found five months later was probably a complication
of the previous surgery and chronic immunosuppression.
23.
a to heterologous and isologous antiplatelet antibodies. Res Vet Sci
Cefoxitin sodium; Merck Sharp, West Point, PA
b 1989;47:288–93.
Doxycycline; Mylan Pharmaceuticals Inc., Morgantown, WV
c 24.
Vitamin K 1; Phoenix Pharmaceuticals Inc., St. Joseph, MO
d
Prednisone; Roxane Laboratories Inc., Columbus, OH 25.
e
Furosemide; Fujisawa USA Inc., Dearfield, IL
f thrombocytopenic purpura. Blood 1994;84(12):4203–8.
Atenolol; Invomed Inc., Dayton, NJ
26.
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3. Peterson JL, Cuoto CG, Wellman ML. Hemostatic disorders in cats:
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Povey RC. Effect of orally administered ribavirin on experimental feline
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Hahn KA, McEntee MF, Daniel GB, Legendre AM, Nolan ML.
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Beale KM, Altman D, Clemmons RR, Bolon B. Systemic toxicosis
associated with azathioprine administration in domestic cats. Am J Vet Res
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Peterson ME, Hurvitz AI, Leib MS, Cavanaugh PG, Dutton RE.
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1984;184:806–8.
O’Keefe DA, Schaeffer DJ. Hematologic toxicosis associated with
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Levy JK. Ataxia in a kitten treated with griseofulvin. J Am Vet Med Assoc
1991;198:105–6.
Gaschen FP, Smith Meyer B, Harvey JW. Amegakaryocytic thrombocy-
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Gabbert NH. Systemic lupus erythematosus in a cat with thrombocytope-
nia. Vet Med/Sm Anim Clin, 1983:77–9.
Vitale CB, Ihrke PJ, Gross TL, Werner LL. Systemic lupus erythematosus
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followed by thrombocytosis in a cat. Feline Pract 1980;10:25–31.
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Cain GR, Cain JL, Turrel JM, Theilen G, Jain NC. Immune-mediated
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Van Vleet JF, Ferrans VJ, Weirich WE. Pathologic alterations in
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Laste NJ, Harpster NK. A retrospective study of 100 cases of feline distal
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Ballem PJ, Seagal GM, Stratton JR, Gernsheimer T, Adamson JW, Slichter
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 Leukoerythroblastosis and
Normoblastemia in the Cat
Over a six-month period, 6% of 313 cats evaluated hematologically had either
leukoerythroblastosis or normoblastemia. Diseases associated with these hematological
conditions included haemobartonellosis, hepatic lipidosis, trauma, viral and bacterial infections,
myeloproliferative disorders, and hemangiosarcoma. The finding of leukoerythroblastosis or
normoblastemia may aid in diagnosing cats presenting with nonspecific signs.
J Am Anim Hosp Assoc 1999;35:471–3.

Alan S. Hammer, DVM, Introduction

Diplomate ACVIM
Maxey Wellman, DVM, PhD,
Diplomate ACVCP
RS
From the North Coast
Veterinary Specialist (Hammer),
6336 North Ridge Road,
Madison, Ohio 44057
and the College of
Veterinary Medicine (Wellman),
The Ohio State University,
Columbus, Ohio 43210.
Address all correspondence and reprint
requests to Dr. Hammer.
The term leukoerythroblastosis (i.e., leukoerythroblastic reaction,
leukoerythroblastic anemia) is defined in veterinary medicine as the pres-
ence of both nucleated red bloods cells (nRBC) and an increased number
of immature myeloid cells in the peripheral blood. In humans,
leukoerythroblastosis is restricted to patients with myelophthisic anemia
where the implication is that the anemia is nonregenerative and release of
red and white cell precursors is due to disruption of normal marrow
architecture. Normoblastemia, or metarubricytosis, is the presence of an
increased number of nRBCs without a left shift. Marked leukocytosis or
anemia is not a necessary component of either leukoerythroblastosis or
normoblastemia in veterinary medicine.
In humans, a variety of disease conditions have been associated with
leukoerythroblastosis and normoblastemia, including blood loss,
hemolytic anemias, solid malignancies, thrombotic microangiopathy, tran-
sient hypoxia, bone marrow necrosis, and myeloproliferative diseases.1–4
Leukoerythroblastosis may also be present in humans as an incidental
reaction to infection, uremia, or cardiac failure and following the use of
granulocyte colony-stimulating factor (G-CSF).1,5
Dogs have a wide variety of disease categories associated with
leukoerythroblastosis and normoblastemia.6 Hematopoietic and nonhema-
topoietic neoplasia were the two largest categories, followed by immune-
mediated hematological disease and trauma. Hemangiosarcoma is the
nonhematopoietic malignancy most often associated with leukoerythro-
blastosis and normoblastemia in the dog.6,7
There is little data concerning leukoerythroblastosis and normoblas-
temia in the cat. Feline leukemia virus (FeLV) infection and lymphoma
have been reported in two cats with leukoerythroblastosis.8 Given the
prevalence of hemotropic parasites, retroviruses, and myeloproliferative
disorders in this species, leukoerythroblastosis and normoblastemia may
be more common than previously thought and may be useful clinical
indicators. This study was performed to determine the prevalence of
leukoerythroblastosis and normoblastemia in cats presenting to a referral
hospital, the disease conditions associated with them, and whether
leukoerythroblastosis carries a poorer prognosis than normoblastemia.
Materials and Methods
Complete blood counts (CBC) performed on 313 cats presenting to the
Veterinary Teaching Hospital-Ohio State University (VTH-OSU) be-
tween July 1, 1992 and December 31, 1992 were evaluated. Total nucle-

JOURNAL of the American Animal Hospital Association 471

472 JOURNAL of the American Animal Hospital Association November/December 1999, Vol. 35

ated cell counts and red blood cell (RBC) parameters

were obtained using an S-Plus IV Coulter a counter, and Table
differential nucleated cell counts were determined by Cats With Leukoerythroblastosis
microscopic evaluation of Giemsa-Wright-stained blood and Normoblastemia
smears. Reticulocytes were stained with new methylene
blue and counted with a hemacytometer. Reticulocyte
Leukoery- Normo-
counts were done only when the packed cell volume Disorder throblastosis blastemia
(PCV) was less than 24%.
Hemobartonellosis 0 4
Normoblastemia was defined as greater than 100
nRBC and 300 or fewer band neutrophils per microliter Hepatic lipidosis 2 2
(µl). Leukoerythroblastosis was defined as greater than Acute trauma 3 0
100 nRBCs/µl and greater than 300 band neutrophils/µl. Upper respiratory 2 0
The medical records of cats with normoblastemia or infection
leukoerythroblastosis were reviewed, and the signal- Myeloproliferative 1 1
disease
ments, hematological values, underlying disease pro-
cesses, treatments, and clinical outcomes were abstracted. Blood loss 0 1
Successful clinical outcome was defined as survival at Hemangiosarcoma 1 0
one month after first detecting either leukoerythro- Mammary carcinoma
blastosis or normoblastemia. Fisher’s exact test was used —chemotherapy 0 1
to determine the prognostic value of leukoerythro- Bacterial abscess 1 0
blastosis versus normoblastemia with regard to survival Obstipation 1 0
at one month.9 A p value of less than 0.05 was consid-
ered significant.
anemia based on reticulocyte numbers; three cats had
Results nonregenerative anemia. Cats with anemia were evenly
Over a six-month time period, 11 cats (3.5%) were found divided between having normoblastemia and leukoery-
to have leukoerythroblastosis, and nine cats (2.8%) had throblastosis.
normoblastemia. The diseases most often associated with Five cats with leukoerythroblastosis died or were
leukoerythroblastosis and normoblastemia were hemo- euthanized; these cats were diagnosed with hepatic lipi-
bartonellosis (n=4), hepatic lipidosis (n=4), acute trauma dosis, myeloproliferative disease, acute trauma, heman-
(n=3), upper respiratory infection (n=2), and myelopro- giosarcoma, and upper respiratory viral infection with
liferative disorders (n=2). No other underlying cause secondary bronchopneumonia. One cat with myelopro-
could be found in any of the cats with hepatic lipidosis. liferative disease and normoblastemia died, and the clini-
Other disorders included chronic blood loss, subcutane- cal outcome at one month in one cat with hepatic lipidosis
ous hemangiosarcoma, mammary carcinoma, bacterial and normoblastemia could not be determined. The re-
abscess, and obstipation secondary to pelvic fractures. maining 13 cats were alive one month after the initial
The cat with mammary carcinoma was receiving doxo- finding of leukoerythroblastosis or normoblastemia. Nine
rubicin and cyclophosphamide chemotherapy at the time of these 13 cats were re-evaluated hematologically at
of the normoblastemia, and there was no evidence of one month, and the leukoerythroblastosis and normoblas-
infiltrative carcinoma in the bone marrow based upon temia had resolved in six cats. Using Fisher’s exact test,
bone marrow aspirate. No other cats were receiving con- there was no significant prognostic difference between
current medication at the time of diagnosis of leuko- cats with normoblastemia or leukoerythroblastosis with
erythroblastosis or normoblastemia. The Table lists the regard to survival at one month (p equals 0.13).
number of cats with leukoerythroblastosis and normo-
blastemia in each disease category. Of the 13 cats tested Discussion
for FeLV and feline immunodeficiency virus (FIV), only Normoblastemia and leukoerythroblastosis appear to be
one was positive for FeLV; that cat had hemobarto- uncommon hematological abnormalities in sick cats, with
nellosis and normoblastemia. a frequency of 6.3% in the population of cats seen at the
The median nRBC number was 550/µl, with a range VTH-OSU between July 1, 1992 and December 31, 1992.
of 130/µl to 16,100/µl. Cats with greater than 2,000 Cats presenting to the VTH-OSU may have more serious
nRBC/µl had hemangiosarcoma, hemobartonellosis, and illnesses and may not be representative of the cat popula-
rhinotracheitis. The median band neutrophil number in tion as a whole. This percentage of 6.3% is similar to the
the cats with leukoerythroblastosis was 1,400/µl, with a percentage of dogs (6%) with leukoerythroblastosis or
range of 600/µl to 3,800/µl (reference range, 0 to 300 normoblastemia in another survey.6
band neutrophils/µl). The median PCV was 21.5% (ref- Normoblastemia and leukoerythroblastosis in the cats
erence range, 24% to 42%). Seven cats had regenerative evaluated as part of this study were associated with
November/December 1999, Vol. 35 Leukoerythroblastosis and Normoblastemia in Cats 473

blood loss and hemolytic anemia; this is similar to dogs prospective studies are needed to determine whether there
and humans. It is interesting to note that normoblastemia is any prognostic value of leukoerythroblastosis and
alone was found in cats with hemobartonellosis. All four normoblastemia in ill cats.
cats with hemobartonellosis in this study had strongly
regenerative macrocytic anemias. Three cats presenting a
Coulter Electronics, Hialeah, FL
with blunt trauma and fractures also had leukoerythro-
blastosis. Splenic contraction or traumatic injury to the
bone marrow with release of red and white cell precur- References
sors may be the mechanism involved. The finding of 1. Clifford GO. The clinical significance of leukoerythroblastic anemia. Med
leukoerythroblastosis and normoblastemia in cats with Clin N Am 1966;50:779–90.
2. Byard RD. Leukoerythroblastosis: a much maligned phenomenon
hepatic lipidosis is unexpected and difficult to explain. It (editorial). J Can Med Assoc 1987;137:191.
may possibly be related to stress or dyserythropoiesis 3. Jandl JH. Aplastic anemias. In: Jandl JH, ed. Blood: textbook of
associated with the liver disease. Twenty-two percent of hematology. Boston: Little, Brown, and Co., 1987:139–42.
cats with hepatic lipidosis in one study had microcyto- 4. Shamdas GJ, Ahmann FR, Matzner MB, Ritchie JM. Leukoerythroblastic
anemia in metastatic prostate cancer: clinical and prognostic significance in
sis;10 the authors found 25% of cats with hepatic lipidosis patients with hormone-refractory disease. Cancer 1993;71:3594–600.
in this study also had microcytosis and normoblastemia. 5. Arici M, Hazendaroglu IC, Erman M, Ozcebe O. Leukoerythroblastosis
The abnormal iron metabolism reported in dogs with following the use of G-CSF. Am J Hematol 1996;52:123–4.
6. Mandell CP, Jain NC, Farver TB. The significance of normoblastemia and
portosystemic vascular shunts may provide a possible leukoerythroblastic reaction in the dog. J Am Anim Hosp Assoc
mechanism as to why some cats with hepatic lipidosis 1989;25:665–72.
have normoblastemia, leukoerythroblastosis, and micro- 7. Shull RM. Inappropriate marrow release of hematopoietic precursors in
three dogs. Vet Pathol 1981;18:569–76.
cytosis. 11
8. Madewell BR, Feldman BF. Characterization of anemias associated with
Extramedullary hematopoiesis is a common mecha- neoplasia in small animals. J Am Vet Med Assoc 1980;176:419–25.
nism for normoblastemia or leukoerythroblastosis in hu- 9. Rosner B. Fundamentals of biostatistics. Boston: PWS-Kent Publishing
mans and dogs.1,6 Extramedullary hematopoiesis was not Co., 1990:341.
10. Center SA, Crawford MA, Guida L, et al. A retrospective study of 77 cats
identified conclusively in any of these cats. Lack of with severe hepatic lipidosis: 1975–1990. J Vet Int Med 1993;7:349–59.
normal bone-marrow stromal barriers is believed to re- 11. Meyer DJ, Harvey JW. Hematologic changes associated with serum and
sult in premature release of cells in extramedullary hepatic iron alterations in dogs with congenital portosystemic vascular
anomalies. J Vet Int Med 1994;8:55–6.
hematopoiesis. Disruption of the normal bone-marrow
12. Bagby GC, Shaw G, Segal GM. Human vascular endothelial cells,
microenvironment by trauma or infiltrative diseases or granulopoiesis, and the inflammatory response. J Inv Dermatol
chemotherapy may result in leukoerythroblastosis or 1989;93:48S–52S.
normoblastemia. Myeloproliferative diseases, tumors
metastatic to the bone marrow (e.g., mammary carci-
noma, lymphoma), or tuberculosis are common causes
of bone-marrow injury and secondary leukoerythro-
blastosis in humans.1,2 Release of red and white cell
precursors may be part of the reaction to a severe stress
or infection. This breakdown in the normal marrow bar-
rier may be the mechanism for leukoerythroblastosis or
normoblastemia in the cats with severe upper respiratory
infection, hepatic lipidosis, and bacterial abscesses in
this study. It is interesting to note that the cat with
hemangiosarcoma in this study had leukoerythroblastosis
similar to that seen in dogs.7 Various cytokines (e.g.,
granulocyte colony-stimulating factor, granulocyte-mac-
rophage colony-stimulating factor, interleukin 1,
interleukin 6) are released by normal endothelial cells,
and if released by neoplastic endothelial cells,
leukoerythroblastosis may result.12 Further studies into
hematological changes in cats with hemangiosarcoma are
needed to determine the prevalence and mechanism of
leukoerythroblastosis in cats with hemangiosarcoma.
When the veterinarian is presented with a cat with
leukoerythroblastosis or normoblastemia, the differen-
tial diagnoses should include hemobartonellosis, heman-
giosarcoma, blood loss, hepatic lipidosis, acute trauma
with fractures, and myeloproliferative disease. Further
 Long-Term Case Study of
Myelodysplastic Syndrome in a Dog
A 10-year-old, female shih tzu was diagnosed as having myelodysplastic syndrome (MDS)
based on the presence of a nonregenerative anemia, dysplastic changes in the three
hematopoietic cell lines, a normal to hypercellular bone marrow, and less than 30% blast cells
of all nucleated cells in the bone marrow. Low-dose aclarubicin, a differentiation-induction
therapy for MDS and atypical leukemias in humans, was administered. Hematological
improvement was observed, and the dog lived for 809 days after the first presentation.
J Am Anim Hosp Assoc 1999;35:475–81.

Tadashi Miyamoto, DVM, PhD Introduction

Toshiaki Horie, DVM
Terumasa Shimada, DVM, PhD
Mitsuru Kuwamura, DVM, PhD
Eiichiroh Baba, DVM, PhD
C dogs with MDS,10,11 one dog died 10 days after initial presentation, one
From the Department of
Veterinary Medicine,
College of Agriculture,
Osaka Prefecture University,
1-1 Gakuencho,Sakai,
Osaka 599-8531, Japan.
Address all correspondence to
Dr. Miyamoto.
Myelodysplastic syndrome (MDS) is comprised of a heterogeneous group
of clonal bone marrow disorders, characterized by cytopenias and faulty
maturation and production in one, two, or all three hematopoietic cell
lines.1–3 A number of MDS cases associated with feline leukemia virus
have been reported in cats,4–9 whereas in dogs only three cases have been
reported.10,11 Prognosis of MDS in the cat and dog is generally poor. Blue,
et al.5 reported that outcomes of MDS in the cat were similar to those of
acute myeloid leukemias (AML); 85% of the cats in each group died or
were euthanized within one week of diagnosis. In three reported cases of
dog was euthanized five weeks after initial presentation, and one dog
developed acute myelomonocytic leukemia 10 weeks after initial presen-
tation and died three weeks later.
There have been few reports about treatments for MDS in dogs or
cats.8,10 Therapies for MDS in humans are also not well established,
despite extensive study. Intensive chemotherapies prescribed for humans
with acute nonlymphocytic leukemia, including corticosteroids or ana-
bolic steroids, are usually ineffective. Supportive therapy with blood trans-
fusion has been the mainstay of treatment for human MDS.12,13 The peripheral
blood cytopenias seen in MDS are considered to be secondary to ineffective
bone marrow hematopoiesis, which is evidenced by disorderly cell line
differentiation; whereas in AML, leukemic cells are recognized as blasts in
which differentiation has stopped.1,2,14 Differentiation-induction therapy,
therefore, is often performed in humans for both the treatment and differ-
entiation of AML and MDS. In cell culture systems, various compounds
such as 1 α, 25-dihydroxy vitamin D3, retinoic acid, low doses of cytosine
arabinoside, or low doses of aclarubicin have been shown to have differ-
entiation-promoting activity.3 Human leukemic cells exposed to these
substances develop morphological, biochemical, and immunological char-
acteristics of their mature counterparts. With induction of terminal differ-
entiation, immature nonfunctional cells lose their proliferative capacity
and enter the postmitotic compartment, thereby reducing the size of the
abnormal clone. Although most of these findings were derived from in
vitro experiments, it has been suggested that differentiation-induction
therapy might be beneficial for the treatment of MDS and AML.3
This paper describes a long-term case study of MDS in a dog that was
treated with a differentiation-induction therapeutic protocol.

JOURNAL of the American Animal Hospital Association 475

476 JOURNAL of the American Animal Hospital Association
Figure 1—Information regarding platelet, red blood cell, and
nucleated cell counts as well as treatments employed in a dog
with myelodysplastic syndrome. The number of arrows and bars
indicates the number of treatments.
Figure 2—Blood smear from the dog with myelodysplastic
syndrome. Notice the dysplastic changes in three hematopoietic
cell lines; ringed nucleated neutrophils (A), Pelger-Huët-like
nuclear anomaly of neutrophils (B), giant neutrophils (C),
binucleated myelocytes (D), nuclear hypersegmentation (E),
abnormally segmented neutrophils (F), and binucleated
metarubricytes (G) (Giemsa-Wright stain, bar=10 µm).
Case Report
A 10-year-old, female shih tzu weighing 4.6 kg was
presented to the Osaka Prefecture University Veterinary
Teaching Hospital with a three-week history of anorexia,
depression, mild diarrhea, and mild polydipsia. The dog
had an anamnesis of bacterial cystitis at four years of
age, otitis externa at six and nine years of age, and a
surgical excision of mammary tumors at nine years of
age. On physical examination, pale mucous membranes
and a slight splenomegaly were noted. A normocytic,
normochromic, nonregenerative anemia (packed cell vol-
ume [PCV], 19%; reference range, 37% to 55%) was
noted [Figure 1; Table 1]. Reticulocytes were less than
1% of red blood cells (RBC) and slight anisocytosis was
November/December 1999, Vol. 35
Figure 3—Bone-marrow smear from the dog with myelodys-
plastic syndrome taken at the same time as the findings in Figure
2. Notice megaloblastoid cells (A) and binucleated erythroblasts
(B) (Giemsa-Wright stain, bar=10 µm).
observed. No other morphological abnormalities of eryth-
rocytes and no nucleated RBCs were seen. Mild leuko-
cytosis (18.6 x10 3/µl; reference range, 6.0 to 17.0
x103/µl) and neutrophil nuclear hypersegmention (3.0
x103/µl) were noted. No blood parasites were observed.
A direct Coombs’ test was negative. An elevated serum
iron level (322 µg/dl; reference range, 94 to 122 µg/dl)
was found. The results of other serum biochemical tests
were within normal reference ranges.
The cause of the anemia could not be identified, and
the PCV value decreased to 12% by day four. The dog
was transfused with crossmatched, fresh, whole blood
and treated with prednisolonea (1 mg/kg body weight,
bid, per os [PO] for 14 days; then 1 mg/kg body weight,
sid, PO for nine days), amoxicillinb (11 mg/kg body
weight, bid, PO for 23 days), and vitamin B complex.c
However, the PCV decreased further to 7% on day 28,
and the anemia remained nonregenerative. Peripheral
blood smears revealed a normocytic, normochromic,
nonregenerative anemia and dysplastic changes in the
three hematopoietic cell lines. Granulocytic lineage ab-
normalities included ringed nucleated neutrophils, a
Pelger-Huët-like nuclear anomaly of neutrophils,
giant neutrophils, binucleated neutrophils, nuclear
hypersegmentation, and abnormally segmented
neutrophils. Binucleated erythroblasts as well as mega-
thrombocytes and micromegakaryocytes were also
seen [Figure 2].
A bone-marrow aspirate was obtained from the proxi-
mal femur and exhibited moderate cellularity with pro-
liferation of erythroid cells, which accounted for 58% of
all nucleated cells (ANC) [Table 2]. There appeared to
be a normal maturation sequence within the myeloid
series. However, a slight increase of myeloblasts was
found, which accounted for 3.7% of nonerythroid cells
(NEC). A high percentage of the myeloid cells were
segmented neutrophils. Megakaryocytes were rarely
noted. Metarubricytes were rarely observed, and the
 Table 1
Hemograms of a Dog With Myelodysplastic Syndrome

Reference
November/December 1999, Vol. 35

Day 0 Day 4 Day 28 Day 45 Day 53 Day 67 Day 130 Day 145 Day 580 Day 597 Day 757 Day 809 Ranges

*PCV (%) 19 12 7 28 18 36 15 36 17 21 11 9 37-55

RBC (x106/µl) 2.91 1.88 1.06 4.25 2.57 5.37 2.17 5.29 2.35 2.78 1.58 1.3 5.5-8.5
Hemoglobin (g/dl) 6.4 4.3 2.5 10.5 6.5 14 5.9 12.7 7.1 7.8 4 3.6 12.0-18.0
MCV (fl) 65.3 63.8 66 65.9 70 67 69.1 68.1 72.3 75.5 69.6 69.2 60.0-77.0
MCHC (%) 33.7 35.8 35.7 37.5 36.1 38.9 39.3 35.3 41.8 37.1 36.4 40 32.0-36.0
Reticulocytes (%) <1 <1 <1 <1 1 1 2 2 1 1 3 <1 0-1.5
Nucleated
RBC/100 WBC 0 0.5 4.5 3 2 0.5 0.5 2 4 1 0.5 0.5 0
WBC (x103/µl) 18.6 26.1 12.6 19.6 5.4 13 16.2 22.2 26.5 30.5 27.9 37.4 6.0-17.0
Band neutrophils (x103/µl) 0.2 1 0.4 0 0.3 0.2 0.2 0 1.2 0.6 0.4 2.8 0-0.3
Segmented neutrophils
(x103/µl) 10.4 17.6 8.5 14 4.1 9 11.5 17 20.3 24.4 21.5 30.5 3.0-11.5
Lymphocytes (x103/µl) 4.5 2.7 1.8 2 0.3 2.5 2.8 3.7 1.6 1.8 2.4 0.9 1.0-4.8
Monocytes (x103/µl) 0.2 2.5 0.6 0.7 0.2 0.5 0.3 0.9 1.1 1.2 1.1 1.3 0.2-1.4
Eosinophils (x103/µl) 0.2 0 0.1 0 0 0.1 0 0 0 0.3 0.6 0 0.1-1.3
Hypersegmented
neutrophils (x103/µl) 3 1 0.5 1.9 0.2 0.5 0.3 0.6 1.1 0.6 0.8 0.7 0
Others (x103/µl) 0.2 1.2 0.8 1.1 0.3 0.2 1.1 0.1 1.3 1.5 1.1 1.1 0
Platelets (x104/µl) 55.7 70.6 24.4 73.7 20 71.7 55.8 65.4 30 20.9 25.4 13.3 20-50
Normal platelets (x104/µl) 54 68.1 19.6 71.9 19.2 68.1 53.8 65.4 27.3 20.5 23.7 13 20-50
Megathrombocytes (x104/µl) 1.7 2.5 4.8 1.8 0.8 3.6 2 0 2.7 0.4 1.7 0.3 0
Megakaryocytes (x104/µl) 0 0 Rare 0 Rare Rare Rare 0 Rare 0 0 0 0

* PCV=packed cell volume; RBC=red blood cells; MCV=mean corpuscular volume; MCHC=mean corpuscular hemoglobin concentration; WBC=white blood cells
Myelodysplastic Syndrome in a Dog
477
478 JOURNAL of the American Animal Hospital Association November/December 1999, Vol. 35

Table 2
Bone Marrow Cell Counts of the Dog With Myelodysplastic Syndrome

Day 28 Day 53 Day 580 Day 809

Erythroid series (%) 58.0 51.5 44.0 25.5

Rubriblasts (%) 2.0 0.5 1.5 7.5
Prorubricytes (%) 16.0 7.0 4.5 6.5
Rubricytes (%) 35.0 40.0 33.0 11.0
Metarubricytes (%) 5.0 4.0 5.0 0.5
Myeloid series (%) 40.0 48.0 56.0 73.0
Myeloblasts (%) 1.5 1.0 2.5 29.0
Promyelocytes (%) 0.5 1.5 1.0 10.5
Myelocytes (%) 1.5 1.5 3.5 16.5
Metamyelocytes (%) 2.5 2.0 2.0 10.0
Band neutrophils (%) 5.0 8.5 2.5 1.5
Segmented neutrophils (%) 28.5 33.0 44.5 5.5
Eosinophils (%) 0.5 0.5 0 0
Other cells (%) 2.0 0.5 0 1.5
Monocytes (%) 0.5 0.5 0 0
Lymphocytes (%) 1.5 0 0 0
Megakaryocytes (%) 0 0 0 1.5
Myeloid/Erythroid ratio 0.69 0.93 1.27 2.86

predominant erythroid cells were prorubricytes and rubri-
cytes. Dysplastic changes such as megaloblastoid cells,
binucleated erythroblasts, ringed nucleated neutrophils,
and nuclear hypersegmented neutrophils were also ob-
served [Figure 3]. Based on peripheral blood and bone
marrow findings, erythropoiesis was judged ineffective.
According to the criteria by the animal leukemia study
group for classification of AML and MDS, 1,2 the periph-
eral blood and bone marrow changes were consistent
with a diagnosis of MDS with erythroid predominance
(MDS-Er) [see Appendix].
On day 28, a crossmatched, whole-blood transfusion
was performed, and the PCV subsequently increased to
35%. Differentiation induction with low-dose cytosine
arabinosided (LD-AraC) was initiated on day 28. Cy-
tosine arabinoside was given at a dose of 10 mg/m2
subcutaneously (SC) twice daily for three weeks. On day
53, the PCV had decreased to 18%. A repeat bone-
marrow sample was obtained from the proximal femur,
and results were similar to those seen on day 28. Since
LD-AraC therapy was considered to have been ineffec-
tive, a third whole-blood transfusion and low-dose
aclarubicine (LD-ACR) therapy, consisting of two
courses (seven-day interval between the two courses),
were performed. Each course of LD-ACR therapy con-
sisted of five days of ACR (5 mg/m2) given daily for a
total cumulative dose of 25 mg/m2. Aclarubicin was
mixed with 50 ml of 5% dextrose in water and given
intravenously [IV] over two hours. Blood examination
was repeated every seven days. Over the next 2.5 months,
there was a gradual reduction of the PCV from 37% to
15% [Figure 1], and the previously identified morpho-
logical changes remained.
On day 130, the PCV had decreased to 15%, a fourth
whole-blood transfusion was performed, and treatment
with LD-ACR (5 mg/m2, sid, consecutively for five days)
was resumed. Subsequently, the dog’s activity and appe-
tite improved and the PCV values remained around 25%
for 15 months, although the cellular dysplastic changes
seen in the peripheral blood did not disappear. On day
253, a mammary tumor was diagnosed and subsequently
surgically removed on day 339. The mammary tissue
was not examined histologically.
On reevaluation on day 580, the PCV had decreased
to 17%. Peripheral blood smears showed persistent dys-
plastic changes in the same three cell lines, which were
similar to those initially observed on day 28. A repeat
bone-marrow aspiration, obtained from the proximal fe-
mur, revealed hypercellularity. The percentages of eryth-
roid cells and myeloblasts in ANC were 44% and 2.5%,
respectively. The dysplastic changes in the three cell
lines continued. Ringed sideroblasts were not found.
Because the blast cells were less than 1% in the periph-
eral blood and less than 5% in the bone marrow, and the
ringed sideroblasts were less than 15%, the dog was
diagnosed as having refractory anemia (RA) in MDS
November/December 1999, Vol. 35
Figure 4—A photomicrograph of the spleen from the dog with
myelodysplastic syndrome. Notice erythroid precursors,
megakaryocytes, and numerous blast cells (Hematoxylin and
eosin stain, bar=50 µm).
[see Appendix]. After an additional whole-blood trans-
fusion and LD-ACR therapy consisting of two additional
courses of five days of ACR (5 mg/m2, sid), the PCV
maintained itself around 23% for approximately six
months.
The mammary tumors relapsed on day 637, and mul-
tifocal masses, suspected to be metastatic lesions, were
observed in the liver by ultrasonography. The PCV had
decreased to 11% and neutrophilia was observed by day
757. The previously identified morphological changes
continued. Supportive therapy consisting of a whole-
blood transfusion, cephalexinf (30 mg/kg body weight,
bid, PO), prednisolone (0.5 mg/kg body weight, bid,
PO), and vitamin B complex were administered on day
757 until the dog was euthanized on day 809.
At necropsy, mammary tumors were found at the
right-fourth (5 cm in diameter) and left-first (2 cm in
diameter) mammary gland. The liver had whitish nod-
ules in the left-lateral lobe (9 by 8 by 6 cm) and right-
lateral lobe (5 cm in diameter). Histopathologically, the
mammary tumors were diagnosed as adenocarcinoma,
and the masses in the liver were metastatic adenocarci-
noma of mammary gland origin. Tumor metastasis was
also found in the lung. The bone marrow was markedly
hypercellular [Table 2]. A large number of myeloid and
erythroid cells and a small number of megakaryocytes
were observed. There was an increased number of both
rubriblasts and myeloblasts. There was also an increased
number of cells at the prorubricyte and rubricyte eryth-
roid stages and the promyelocyte and myelocyte myeloid
stages. Very few segmented neutrophils were evident,
and there was a decreased number of metarubricytes.
These findings suggested both ineffective erythropoiesis
and myelopoiesis with maturation arrest. These bone
marrow findings were consistent with refractory anemia
with excess of blasts in transformation (RAEB-t) in MDS
[see Appendix]. There was a large number of immature
Myelodysplastic Syndrome in a Dog 479
Appendix
The Classification and the Summary of
Diagnostic Criteria of the Myelodysplastic
Syndromes (MDS)1,2,14
Pan(bi)cytopenia with dyserythropoiesis,
dysgranulopoiesis, and/or dysmegakaryopoiesis
1) Refractory anemia (RA): Blast cells ≤1% in
peripheral blood (PB), <5% in bone marrow (BM).
2) Refractory anemia with ringed sideroblasts (RARS):
Ringed sideroblasts ≥15% in BM, blast cells ≤1% in
PB, <5% in BM.
3) Refractory anemia with excess of blasts (RAEB):
Blast cells 1%–5% in PB, 5%–20% in BM.
4) Chronic myelomonocytic leukemia (CMMoL):
Monocytes and promonocytes >1,000/µl in PB,
blast cells <5% in PB, ≤20% in BM.
5) Refractory anemia with excess of blasts in
transformation (RAEB-t): Blast cells ≥5% in PB,
20%–30% in BM, or presence of Auer rods.
6) Myelodysplastic syndrome with erythroid
predominance (MDS-Er): Erythroid cells >50% in
BM, blast cells <30% in BM.
myeloid cells, erythroid cells, and megakaryocytes in the
spleen and lymph nodes as well as in the bone marrow
[Figure 4]. A small number of hematopoietic cells were
also observed in the liver.
Discussion
French-American-British (FAB) classification has been
proposed as specific criteria for identification and
classification of AML and MDS in dogs and cats.1
Myelodysplastic syndrome is characterized by single or
multiple cytopenias together with morphological changes
in the three peripheral blood and bone-marrow cell lines;
a normal to hypercellular bone marrow; ineffective hem-
atopoiesis; and elevated but less than 30% blast cells of
ANC in the bone marrow. 1,2 The present case was char-
acterized by a nonregenerative anemia, normocellular to
hypercellular bone marrow, and dysplastic changes in all
hematopoietic cell lines. Dyserythropoiesis was distinc-
tive with binucleated erythroblasts and megaloblastoid
cells. Dysgranulopoiesis was characterized by ringed
nucleated neutrophils, Pelger-Huët-like nuclear anomaly
of neutrophils, giant neutrophils, binucleated neutrophils,
nuclear hypersegmentation, and abnormally segmented
neutrophils. Morphological features of dysthrombopoiesis
included megathrombocytes and micromegakaryocytes.
An increased number of blast cells, which was less than
30% of ANC, were also found in the bone marrow.
Based on these findings, the patient was diagnosed as
having a MDS.
According to the FAB classification in humans,14
MDS is further divided into five types: RA, refractory
anemia with ringed sideroblasts (RARS), refractory ane-
480 JOURNAL of the American Animal Hospital Association
mia with excess of blasts (RAEB), chronic myelomono-
cytic leukemia (CMMoL), and RAEB-t. Myelodysplastic
syndrome with erythroid predominance has been added
by the animal leukemia study group for classification of
AML and MDS1,2 [see Appendix]. The individual syn-
dromes are differentiated on the basis of the percentage
of blast cells in the peripheral blood and bone marrow,
percentage of ringed sideroblasts in the bone marrow,
presence of monocytosis in the peripheral blood, and the
number of cell lines showing dysplastic changes.
Myelodysplastic syndrome is considered to be a preleu-
kemic state of the bone marrow, and there is a possibility
of development into AML.1,2,7,8,14 The present dog was
diagnosed as having MDS-Er on day 28, which pro-
gressed to RAEB-t as defined by bone marrow findings
seen at postmortem examination.
Aclarubicin is an anthracycline with a potent cyto-
static effect on leukemias, lymphomas, and other neo-
plasms. In addition to its cytostatic effect, low-dose
concentrations of ACR are reported to have a cell-differ-
entiation or maturation effect on some human myeloid
cell lines and freshly isolated human leukemic cells in
vitro.3,13 Aclarubicin also increases expression of eryth-
roid transcription factors and erythroid genes in human
erythroleukemic cells.15 Clinical trials of low-dose ad-
ministration of ACR in humans with MDS and AML
have been reported, and a differentiation-inducing effect
has been demonstrated.12,13,16,17 Harada, et al. 17 reported
outcomes in 18 human patients who had received LD-
ACR therapy; in 11 RAEB/RAEB-t patients, two had
complete remissions and four had partial remissions,
while in seven RA patients two partial remissions were
seen. Furthermore, since some nonresponders to LD-
AraC therapy did respond to LD-ACR therapy, they
suggested that LD-ACR therapy could be used if the
initial treatment with LD-AraC fails. Shibuya, et al.13
reported outcomes in nine human patients who had re-
ceived LD-ACR therapy; complete remission was
achieved in three of three patients with RAEB-t, partial
remission was obtained in one of three patients with
RAEB, and hematological improvement was noted in
one of three patients with RA. Furthermore, in vitro
studies indicated that ACR induced differentiation of
immature bone-marrow cells into mature neutrophils
from one patient with MDS.16
In the case of this report, treatment with whole-blood
transfusion alone or in combination with LD-AraC
therapy was not effective. After treatment with whole-
blood transfusion and two courses of LD-ACR therapy,
the PCV was maintained at 20% to 30% for 2.5 months.
Subsequently, another whole blood transfusion and one
further course of LD-ACR therapy was required to main-
tain the PCV at 25% for an additional 15 months; the
anemia and dysplastic changes in the blood persisted
throughout; however, relapse occurred at day 580, ne-
cessitating an additional whole-blood transfusion and
November/December 1999, Vol. 35
two courses of LD-ACR therapy, which then maintained
the PCV around 23% for an additional six months. As
the ACR treatment in this dog was coincident with the
administration of blood, and no bone-marrow examina-
tion was performed after the ACR was given, it is diffi-
cult to estimate the effects of ACR. The authors conclude
that the RA was resistant to treatment with whole-blood
transfusion and LD-AraC therapy; however, the RA was
benefited by treatments with whole-blood transfusion
and LD-ACR therapy.
Side effects of LD-ACR therapy in humans include
nausea, vomiting, anorexia, and mild hepatopathy.12,13,16,17
During the course of treatment, the dog in this study
experienced no side effects or complications. However,
further studies on the safety and effects of ACR in dogs
and cats must be undertaken.
To the authors’ knowledge, the treatment with LD-
ACR for MDS in dogs and cats has not been reported.
This case report suggests that LD-ACR therapy may be a
potential strategy in the treatment of MDS. The optimal
dose and schedule of ACR for the treatment of AML or
MDS in animals are still uncertain. Further studies with
more widely ranging clinical trials are needed.
a
Prednisolone; Takeda Chemical Industries, Ltd, Osaka, Japan
b
Pasetocin; Kyowa Hakko Kogyo Co. Ltd, Tokyo, Japan
c
Neurovitan; Fujisawa Pharmaceutical Co. Ltd, Osaka, Japan
d
Cylocide; Nippon Shinyaku Co. Ltd, Kyoto, Japan
e
Aclacinon; Yamanouchi Pharmaceuticals Co. Ltd, Tokyo, Japan
f
Larixin; Toyama Chemical Co. Ltd, Tokyo, Japan
References
1. Jain NC, Blue JT, Grindem CB, et al. Proposed criteria for classification of
acute myeloid leukemia in dogs and cats. Vet Clin Pathol 1991;20:63–82.
2. Raskin RE. Myelopoiesis and myeloproliferative disorders. Vet Clin N Am
Sm Anim Pract 1996;26:1023–42.
3. Aul C, Gattermann N. The role of low-dose chemotherapy in
myelodysplastic syndromes. Leukemia Res 1992;16:207–15.
4. Baker RJ, Valli VEO. Dysmyelopoiesis in the cat: a hematological disorder
resembling refractory anemia with excess blasts in man. Can J Vet Res
1986;50:3–6.
5. Blue JT, French TW, Kranz JS. Non-lymphoid hematopoietic neoplasia in
cats: a retrospective study of 60 cases. Cornell Vet 1988;78:21–42.
6. Jain NC. Classification of myeloproliferative disorders in cats using criteria
proposed by the animal leukemia study group: a retrospective study of 181
cases (1969–1992). Comp Hematol Int 1993;3:125–34.
7. Miyamoto T, Hachimura H, Noguchi M, Amimoto A. A feline case of
myelodysplastic syndrome-Erythroblastic (MDS-Er). J Jpn Vet Med Assoc
1996;49:560–2 (Japanese with English abstract).
8. Shimada T, Matsumoto Y, Okuda M, et al. Erythroleukemia in two cats
naturally infected with feline leukemia virus in the same household.
J Vet Med Sci 1995;57:199–204.
9. Testa NG, Orions DE, Lord BI. A feline model for the myelodysplastic
syndrome: pre-leukemic abnormalities caused in cats by infection with a
new isolate of feline leukemia virus (FeLV), AB/GM1. Hematologica
1988;73:17–20.
10. Couto CG, Kallet AJ. Preleukemic syndrome in a dog. J Am Vet Med
Assoc 1984;184:1389–92.
11. Weiss DJ, Raskin R, Zerbe C. Myelodysplastic syndrome in two dogs.
J Am Vet Med Assoc 1985;187:1038–40.
November/December 1999, Vol. 35
12. Shibuya T, Morioka E, Taniguchi S, Ohhara N, Okamura S, Niho Y.
Treatment of four patients with myelodysplastic syndrome with a small
dose of aclacinomycin-A. Leukemia Res 1987;11:851–4.
13. Shibuya T, Teshima T, Harada M, et al. Treatment of myelodysplastic
syndrome and atypical leukemia with low-dose aclarubicin. Leukemia Res
1990;14:161–7.
14. Bennett JM, Catovsky D, Daniel MT, et al. Proposals for the classification
of the myelodysplastic syndromes. Br J Haematol 1982;51:189–99.
Myelodysplastic Syndrome in a Dog 481
15. Morceau F, Aries A, Lahlil R, et al. Evidence for distinct regulation
processes in the aclacinomycin- and doxorubicin-mediated differentiation
of human erythroleukemic cells. Biochem Pharmacol 1996;51:839–45.
16. Sato S, Sakashita A, Ishiyama T, et al. Possible differentiation treatment
with aclacinomycin A in acute myelomonocytic leukemia refractory to
conventional chemotherapy. Anticancer Res 1992;12:371–6.
17. Harada M, Shibuya T, Teshima T, et al. A randomized phase ΙΙ trial of
low-dose aclarubicin vs very low-dose cytosine arabinoside for treatment of
myelodysplastic syndrome. Leukemia Res 1993;17:629–32.
 Paraneoplastic Thrombocytosis-Induced
Systemic Thromboembolism in a Cat
A six-year-old cat presented with clinical signs consistent with distal aortic thromboembolism
while clinical signs of cardiovascular disease were absent. Diagnostics, including thoracic
radiographs, electrocardiography, and echocardiography revealed no cardiovascular
anomalies. Thoracic radiographs revealed multifocal pulmonary lesions consistent with
neoplasia. Complete blood cell count demonstrated a marked thrombocytosis, leukopenia, and
neutropenia. Histopathology of the pulmonary lesions confirmed multiple bronchoalveolar
carcinomas. Myelodysplasia with megakaryocytic hyperplasia and ineffective myelopoiesis was
noted on bone-marrow histopathology from multiple sites. The absence of other causes
suggested a paraneoplastic thrombocytosis. The diagnosis of paraneoplastic thrombocytosis-
induced thromboembolism was made due to the lack of underlying cardiac disease and the
presence of a marked thrombocytosis. The presence of thrombocytosis and thromboembolism
associated with neoplasia is discussed. J Am Anim Hosp Assoc 1999;35:483–6.

Daniel F. Hogan, DVM, Case Report

Diplomate ACVIM
Ravinder S. Dhaliwal, DVM,
Diplomate ACVIM
D. David Sisson, DVM,
Diplomate ACVIM
Barbara E. Kitchell, DVM, PhD,
Diplomate ACVIM
(Oncology, Internal Medicine)
C The EKG and echocardiogram were normal. The nuclear perfusion
From the Department of
Veterinary Clinical Medicine,
University of Illinois,
1008 West Hazelwood Drive,
Urbana, Illinois 61802.
Address all reprint requests to Dr. Hogan.
A six-year-old, 4.8-kg, male, castrated domestic shorthair presented to the
Small Animal Clinic at the University of Illinois Veterinary Medical
Teaching Hospital (UI-VMTH) for evaluation of hind-limb paralysis of
three hours duration. Pertinent physical examination findings included
cool hind limbs with no palpable femoral pulses, absent segmental re-
flexes, and no response to deep pain. There was a notable lack of cardio-
vascular abnormalities on the physical examination, with no murmurs,
gallops, or distinct signs of congestive heart failure. Diagnostic testing
included a complete blood cell count (CBC), serum biochemistry profile,
feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV)
tests, thoracic radiographs, an electrocardiogram (EKG), echocardiog-
raphy, and a nuclear perfusion study using free (i.e., unbound) Tc99m.
study demonstrated abrupt blockage of aortic flow immediately distal to
the left kidney, with some collateral circulation to the hind limbs consis-
tent with an aortic thromboembolus. There were multifocal, interstitial to
alveolar areas noted on thoracic radiographs, with no significant cardio-
vascular changes [Figures 1A, 1B]. Abnormalities on serum biochemistry
profiling included hyperproteinemia (8.5 gm/dl; reference range, 5.8 to
7.8 gm/dl), hyperglycemia (160 mg/dl; reference range, 65 to 129 mg/dl),
hypercholesterolemia (163 mg/dl; reference range, 63 to 130 mg/dl), and
hypokalemia (3.1 mEq/L; reference range, 3.8 to 5.0 mEq/L). The CBC
revealed marked thrombocytosis (1,026 x103/µl; reference range, 300 to
700 x103/µl), leukopenia (2.82 x103/µl; reference range, 5.5 to 19.5 x10 3/
µl), neutropenia (0.554 x103/µl; reference range, 2.5 to 12.5 x103/µl), and
a marginal normocytic normochromic anemia (hematocrit, 29.7%; refer-
ence range, 30% to 45%). Examination of the peripheral blood smear
confirmed an increased number of normal-appearing platelets. Retroviral
tests were negative.
A tentative diagnosis of paraneoplastic thrombocytosis-induced aortic
thromboembolization was made. Pulmonary neoplasia was suspected, but

JOURNAL of the American Animal Hospital Association 483

484 JOURNAL of the American Animal Hospital Association
Figure 1A
Figures 1A,1B—Lateral (1A) and ventrodorsal (1B) thoracic
radiographs in a six-year-old cat with aortic thromboembolism
demonstrating multifocal pulmonary lesions (arrows).
Figure 1B
other inflammatory diseases or pulmonary thromboem-
bolic lesions could not be ruled out. The clients were
informed of the tentative diagnosis, and a guarded prog-
nosis was given. A therapeutic plan of thrombolytics and
supportive care was offered along with continued diag-
nostics to confirm the etiology of the pulmonary lesions.
The owners elected euthanasia due to monetary and per-
sonal concerns.
November/December 1999, Vol. 35
Figure 2—Photomicrograph of a pulmonary lesion from the cat
in Figure 1, demonstrating a neoplastic epithelial population
forming papillary structures (arrow) contrasted to the more
normal lung tissue (top right) (Hematoxylin and eosin stain;
500X).
Figure 3—Photomicrograph of bone marrow from the cat in
Figure 1, demonstrating hyperplasia of megakaryocytes (arrows)
and a marked decrease in the myeloid/erythroid ratio with an
almost complete absence of marrow granulocyte reserves. There
is also a marked early asynchrony of the myeloid cell line with a
predominance of myeloblasts (arrowheads) (Hematoxylin and
eosin stain; 1,000X).
Gross necropsy findings confirmed an aortic throm-
boembolus at the aortic trifurcation. Firm, slightly raised,
pale lesions varying from 10 to 14 mm in diameter were
noted in the left-caudal, left-cranial, and right-caudal
lung lobes. Histopathology of the pulmonary lesions re-
vealed multiple bronchoalveolar carcinomas [Figure 2].
There were no structural cardiac changes identified. Re-
nal changes consisted of marked, chronic, membranous
glomerulopathy. Examination of bone marrow from the
femur and rib demonstrated myelodysplasia with hyper-
plasia of the megakaryocytic line and ineffective my-
elopoiesis [Figure 3].
Discussion
Thrombocytosis in cats is defined as elevation of the
platelet count above 700 x103/µl. Initial differential di-
agnoses for thrombocytosis included essential thrombo-
cythemia, chronic myeloproliferative diseases (MPDs)
(such as myelofibrosis and chronic myelogenous leuke-
November/December 1999, Vol. 35
mia), acute megakaryoblastic leukemia, solid neoplasms,
and secondary thrombocytosis due to acute or chronic
inflammatory conditions.1,2 Other possible causes of
thrombocytosis include physiological (i.e., exercise, epi-
nephrine), postsplenectomy, iron deficiency, and rebound
thrombocytosis following a thrombocytopenic episode.3–5
The term thrombocythemia or autonomous (i.e., primary)
thrombocytosis is used to describe an increased platelet
count in patients with MPDs. Thrombocytosis in patients
with other diseases is referred to as reactive or secondary
thrombocytosis.
In human patients, paraneoplastic thrombocytosis is
often associated with carcinomas of the pancreas, lung,
gastrointestinal tract, ovary, and breast.6 The etiology of
thrombocytosis in most cancer patients is unknown, al-
though paraneoplastic overproduction of thrombopoietin
or thrombopoietin-like substances has been suggested.5
In a study of 118 dogs and 17 cats with thrombocytosis,
the most common disease categories associated with
thrombocytosis were neoplasia (25%), gastrointestinal
disorders (19%), and endocrine disorders (10%). 7
Corticosteroids and antineoplastic agents were the
most common drug classes clinically associated with
thrombocytosis in the same study. Thrombocytosis sec-
ondary to azathioprine and doxorubicin has been
reported in cats, with up to a 31% incidence in cats
treated with doxorubicin. 8,9 In the present case, a diagno-
sis of reactive thrombocytosis as a paraneoplastic syn-
drome secondary to pulmonary carcinoma was made
based on the exclusion of other causes of thrombocyto-
sis. Bone marrow from two different sites (i.e., rib and
femur) showed no evidence of myeloproliferative dis-
ease. Essential thrombocythemia was ruled out based on
the absence of circulating megakaryoblasts and bone-
marrow histopathology.1 Iron deficiency anemia-induced
thrombocytosis seems unlikely based on the normal mean
corpuscular volume (MCV), mean corpuscular hemoglo-
bin concentration (MCHC), and lack of hypochromasia
on the CBC, although serum iron levels and total iron-
binding capacity (TIBC) were not measured in this case.
Epinephrine-induced thrombocytosis cannot be com-
pletely ruled out due to the lack of serial CBC evalua-
tions, but there was no evidence of a stress leukogram in
this cat. There was also no history of thrombocytopenia
as a cause of rebound thrombocytosis.
Paraneoplastic thromboembolism in humans (i.e.,
Trousseau’s syndrome) has been associated more with
neoplasia of the pancreas, lung, and gastrointestinal
tract.10 The correlation between thrombocytosis and in-
creased platelet aggregability has generally been poor;
therefore, the clinical risk of thrombocytosis-induced
thromboembolism remains unclear.6 Platelet aggrega-
tion studies have revealed increased platelet function in
dogs with malignancies.11 It is unknown if cats demon-
strate these same changes, and these studies were not
performed in this cat nor was coagulation profiling done.
Systemic Thromboembolism in a Cat 485
If there is concurrent increased platelet aggregability in
the presence of thrombocytosis, it would appear the risk
for thromboembolic events would be high. In a large
study of distal aortic thromboembolization in cats, a
small number had concurrent focal pulmonary lesions,
suggesting a possible association.12
There was marked, chronic glomerulopathy on renal
histopathology, although hypoalbuminemia was not
noted on serum biochemistry. Nephrotic syndrome has
been associated with an increased risk of thromboembo-
lism through antithrombin-III deficiency along with
increased platelet aggregability.13,14 Urine was not sub-
mitted to determine a protein-to-creatinine ratio nor were
antithrombin III levels measured; therefore, the severity
and potential role of glomerular disease cannot be as-
sessed in this cat.
Systemic arterial thromboembolization in the cat is
usually associated with some form of myocardial disease
such as hypertrophic cardiomyopathy, restrictive car-
diomyopathy, or dilated cardiomyopathy.15,16 Throm-
boemboli are thought to originate from a dilated left
auricle or atrium, with the left ventricular apex repre-
senting a less common site. Emboli travel downstream in
the systemic circulation to that point where their size
exceeds vessel diameter. The most common site of oc-
clusion is the aortic trifurcation; but brachial, cerebral,
renal, and splanchnic embolizations have also been re-
ported. Clinical signs are dependent on the site of
vascular occlusion. Distal aortic thromboembolization
classically presents with pelvic-limb paresis/paralysis,
loss of femoral pulses, cool pelvic limbs with firm pel-
vic-limb muscle groups, loss of deep pain, and absence
of segmental reflexes. Many cats do not survive the
initial thromboembolic episode, and those that do often
suffer reembolization.
The cat reported here exhibited clinical signs consis-
tent with distal aortic thromboembolization. The lack of
abnormalities noted on cardiac examination, normal
echocardiographic study, and lack of significant cardio-
vascular changes on thoracic radiographs suggested a
noncardiac cause for the thromboembolic event. In this
cat, the only identifiable abnormalities were pulmonary
neoplasia and thrombocytosis.
To the authors’ knowledge, this is the first reported
case of reactive thrombocytosis secondary to pulmonary
carcinoma in a cat. Further, this is the first reported case
of paraneoplastic thrombocytosis-induced systemic
thromboembolism in a cat. Cats presenting with classic
clinical signs of systemic arterial thromboembolism with
lack of significant cardiac pathology should prompt fur-
ther evaluation for possible underlying neoplasia.
Acknowledgment
The authors wish to thank Joanne B. Messick, VMD,
PhD, Diplomate ACVP for her assistance in pathology
interpretation.
486 JOURNAL of the American Animal Hospital Association November/December 1999, Vol. 35

References 9. O’Keefe D, Schaeffer DJ. Hematologic toxicosis associated with

doxorubicin administration in cats. J Vet Int Med 1992;6(5):276–83.
1. Hammer AS, Couto CG, Getzky D, Bailey MQ. Essential thrombocythemia
10. Heffner RR. Myopathy of embolic origin in patients with carcinoma.
in a cat. J Vet Int Med 1990;4(2):87–91.
Neurology 1971;21:840–3.
2. Burton S, Miller L, Horney B, Marks C, Shaw D. Acute megakaryoblastic
11. McNiel EA, Ogilvie GK, Fettman MJ, Salman MD. Platelet hyperfunction
leukemia in a cat. Vet Clin Path 1996;25(1):6–9.
in dogs with malignancies. J Vet Int Med 1997;11(3):178–82.
3. Bithell TC. Thrombocytosis. In: Lee GR, Bithell TC, Forester J, Athens
12. Laste NJ, Harpster NK. A retrospective study of 100 cases of feline
JW, Lukens TN, eds. Wintrobe’s clinical hematology. 9th ed. Philadelphia:
distal aortic thromboembolism: 1977–1993. J Am Anim Hosp Assoc
Lea & Febiger, 1993:1390–6.
1995;31:492–500.
4. Helfand SC. Platelets and neoplasia. Vet Clin N Am (Sm Anim Pract)
13. Green RA, Russo EA, Greene RT, Kabel AL. Hypoalbuminemia-related
1988;18(1):131–56.
platelet hypersensitivity in two dogs with nephrotic syndrome. J Vet Med
5. John WJ, Foon KA, Patchell RA. Paraneoplastic syndromes. In: DeVita Assoc 1985;186(5):485–8.
VT, Hellman S, Rosenberg SA, eds. Cancer: principles and practice of
14. Green RA, Kabel AL. Hypercoagulable state in three dogs with nephrotic
oncology. 5th ed. Philadelphia: Lippincott-Raven, 1997:2397–422.
syndrome: role of acquired antithrombin III deficiency. J Am Vet Med
6. Bick RL, Strauss JF, Frenkel EP. Thrombosis and hemorrhage in oncology Assoc 1982;181(9):914–7.
patients. Heme Onc Clin N Am 1996;10(4):875–907.
15. Harpster NK. Feline myocardial diseases. In: Kirk RW, ed. Current
7. Hammer AS. Thrombocytosis in dogs and cats: a retrospective study. veterinary therapy IX. Philadelphia: WB Saunders, 1986:380–98.
Comp Hematology Int 1991;1(4):181–6.
16. Bonagura JD, Fox PR. Restrictive cardiomyopathy. In: Bonagura JD, ed.
8. Beale KM, Altman D, Clemmons RR, Bolon B. Systemic toxicosis Kirk’s current veterinary therapy XII. Philadelphia: WB Saunders,
associated with azathioprine administration in domestic cats. Am J Vet Res 1995:863–7.
1992;53(7):1236–40.
 Primary Hypothyroidism Associated
With Leishmaniasis in a Dog
A case of primary hypothyroidism associated with leishmaniasis is described in a four-year-old,
male Yorkshire terrier. Clinical diagnosis of hypothyroidism was confirmed by a low baseline
serum tetraiodothyronine (T4), a reduced response to thyroid-stimulating hormone (TSH)
stimulation, an increased serum TSH concentration, and scintigraphic thyroid gland
examination. Examination of a thyroid biopsy showed many Leishmania amastigotes, both
inside and outside of macrophages, together with signs of follicular atrophy.
J Am Anim Hosp Assoc 1999;35:487–92.

L. Cortese, DVM Introduction

G. Oliva, DVM, PhD
P. Ciaramella, DVM
A. Persechino, DVM, PhD
B. Restucci, DVM
C Canine leishmaniasis, which is caused by Leishmania infantum, is charac-
Endocrine disorders associated with protozoal infections have been de-
scribed both in humans 1 and in animal species. In experimentally induced
trypanosomal infections in small ruminants,2–4 abnormalities were identi-
fied within the hypothalamic-pituitary axis, the thyroid and adrenal glands,
and the reproductive tract. Thyroid dysfunction may be related to para-
sitic action as well as to the operation of complex mechanisms, such as
chronic stress and massive release of specific cytokines, capable of im-
pairing pituitary hormone secretion.3,4 Canine leishmaniasis (CanL) is a
common parasitic disease in all the countries of the Mediterranean area.
terized by the following signs and clinical laboratory abnormalities:
lymphadenomegaly, splenomegaly, pale mucous membranes, weight loss,
dry exfoliative dermatitis, onychogryphosis, epistaxis, anemia, hyper-
globulinemia, hypoalbuminemia, and thrombocytopenia. To date, no en-
docrine disorders have been reported in dogs infected with Leishmania
spp. The purpose of this report is to describe the clinical, laboratory,
biopsy, and postmortem findings in a case of primary hypothyroidism
associated with leishmaniasis in a dog.

From the Sezione di Clinica Medica
Veterinaria – Dipartimento di Scienze
Cliniche Veterinarie (Cortese, Oliva,
Ciaramella, Persechino), and the
Dipartimento di Patologia e
Sanità Animale (Restucci),
Università degli Studi di Napoli “Federico II,”
via Delpino n°1,
80137 Napoli, Italy.
Address all correspondence to Dr. Cortese.
Case Report
A four-year-old, male Yorkshire terrier weighing 5 kg, was referred to the
authors’ clinic for further evaluation. The dog had been living with his
owner since two months of age and had received regular annual vaccina-
tions and antihelmintic treatment. The owner reported that for the past
eight months, the dog had started to progressively lose hair and 1.8 kg of
its body weight. During this period, the dog was seen by several practi-
tioners who tried various treatments (e.g., cephalexin, dexamethasone,
and griseofulvin) without success.
Physical examination revealed emaciation, a generalized decrease in
muscle mass, depression, and weakness. The dog was anorexic, reluctant
to move, and had a slow, uncertain gait. The skin examination showed
areas of alopecia on the back, the ears, and the tail (called “mouse tail”),
with widespread scaling which was nonpruritic [Figure 1]. In nonalopecic
areas, hair was dull and epilated easily. Fistulas were seen in the perianal
region, and there was a large ulcer in the right carpal region, as well as
onychogryphosis and scrotal and sternal edema. Pale mucous membranes
were observed, and the lymph nodes (especially in the prescapular region)
were enlarged. The temperature was 37.8˚ C, the femoral pulse was slow

JOURNAL of the American Animal Hospital Association 487

488 JOURNAL of the American Animal Hospital Association
Figure 1—Skin of a four-year-old, male Yorkshire terrier
diagnosed with Leishmania infection and hypothyroidism. Areas
of alopecia and onychogryphosis are evident.
at 60 beats per minute, and the breathing rate was normal
at 20 breaths per minute. There was unilateral keratocon-
junctivitis sicca (KCS) with hyperemia, chemosis of the
conjunctivae, and irregularities of the corneal surface;
Schirmer tear testa values were 2 mm wetting per minute.
Routine hematology and serum biochemistry were
performed with results provided in Tables 1 and 2. Ab-
normal laboratory findings included a normochromic
and normocytic nonregenerative anemia, hypercholes-
terolemia, marked hypoalbuminemia, and a polyclonal
gammopathy. The immunofluorescence test for Leish-
mania-specific antibodies (IFAT) yielded a positive titer
of 1/640, and the diagnosis of leishmaniasis was con-
firmed by the observation of many amastigotes, both
inside and outside of macrophages, in preparations ob-
tained from the lymph nodes and bone marrow. Parasite
density in smears, determined according to the method
described in previous papers,5 was 5+ (10 to 100
amastigotes in a 1,000 power microscopic field) [Table
2]. Thyroid function was evaluated by determination of
the baseline serum tetraiodothyronine (T4) concentration
by radioimmunoassay (RIA) using a solid-phase com-
mercial kit.b A thyroid-stimulating hormone (TSH)
stimulation test was performed by intravenous (IV) ad-
ministration of 0.4 IU of thyrotropin,c with a serum T4
concentration assayed six hours later. The plasma thy-
roxin level was below the reference range (0.4 µg/dl;
reference range, 1.6 to 3.4 µg/dl). Although it increased
after the administration of TSH (1 µg/dl), it did not
obtain values indicative of a euthyroid state (greater than
1.9 µg/dl) [Table 3]. Baseline serum concentration of
TSH was determined using a homologous canine TSH
assay.d The TSH serum concentration was above the
reference range (0.9 ng/ml; reference range, less than 0.3
ng/ml) [Table 3]. As tumor necrosis factor-α (TNF-α)
interferes with thyroid function in some neoplastic, bac-
terial, and parasitic diseases,3,4 the authors measured it
by means of a bioassay employing recombinant human
November/December 1999, Vol. 35
Figure 2—Dorsoventral view of pertechnetate (99mTc) scan
performed in the dog from Figure 1. Uptake of 99mTc is normal by
the parotid salivary glands (large arrows), which are readily
visible, but it is markedly reduced by the thyroid lobes (small
arrows), which are barely visible. Highest uptake is indicated by
red color.
TNF-α. e Serum concentration of TNF-α was 6,067.73
pg/ml, high when compared to the canine reference range
of 0 to 120 pg/ml, according to the Department of Immu-
nology, Faculty of Veterinary Medicine of Utretch. In
addition, electrocardiography and radiolabeled Techne-
tium (99mTc) scintigraphy of the cervicofacial region
were performed. Electrocardiography showed hypovolt-
age of QRS complexes in lead II (height of R wave in
lead II, less than 0.5 mv; reference range in small canine
breeds, 0.5 to 2.5 mv), combined with sinus bradycardia
(60 beats per minute; normal value in toy breeds, 100 to
180 beats per minute) and signs of myocardial hypoxia
(S-T segment depression). On scintigraphy, a marked
reduction in uptake and concentration of 99mTc within
the thyroid gland was found when compared with the
uptake and concentration of salivary glands [Figure 2].
Findings were consistent with a diagnosis of hypothy-
roidism; euthyroidism and euthyroid sick syndrome were
eliminated.6
Biopsy specimens were obtained from the thyroid
gland and from the skin at the level of the dorsolumbar
region, peripherally to an alopecic area. The samples
were fixed in 10% buffered formalin and embedded in
paraffin wax. The 5-µm thick sections were stained with
hematoxylin and eosin; for the skin sections, Alcian
blue-periodic acid-Schiff (PAS) stain was also used. His-
topathological examination of the thyroid gland biopsies
revealed dilated follicles which were filled with colloid,
within which the thyroid cells appeared strongly flat-
tened. In adjacent areas, some follicles showed decreased
size and colloid content while others showed total dis-
ruption of their normal architecture. In some sections,
complete follicular atrophy was also found. No inflam-
matory cells were seen. In all sections examined, espe-
cially in the thicker interstitial spaces, amastigotes inside
macrophages were found together with free parasitic forms
November/December 1999, Vol. 35 Leishmaniasis in a Dog 489

Table 1
Hematological and Serum Biochemical Data From a Four-Year-Old Yorkshire Terrier
With Leishmania Infection and Hypothyroidism

Hematological Values* Serum Biochemical Values

Hb g % 8.9 (13.5–18) Urea mg/dl 48.8 (25–50)
RBC x106/µl 3.8 (5.5–8.5) Glucose mg/dl 82.0 (60–110)
PCV % 25.8 (35–45) Creatinine mg/dl 0.1 (<1.8)
MCV µ3 67.8 (60–77) AST U/L 35.2 (5–45)
MCH pg 23.4 (20–24.5) ALT U/L 23.7 (10–47)
MCHC % 34.5 (31–34) ALP U/L 156.0 (<180)
Reticulocytes % 0.2 (0.0–1.5) Total bilirubin g/dl 0.4 (0.10–0.5)
WBC x103/µl 26.1 (6–17) Total cholesterol mg/dl 300.0 (136–270)
Lymphocytes % 13.0 (12–30) Triglycerides mg/dl 120.0 (20–60)
Monocytes % 1.0 (3–9) CK U/L 53.0 (<50)
Neutrophils % 86.0 (60–75) LDH U/L 107.0 (<100)
Eosinophils % 0.0 (2–10)
Basophils % 0.0 (0–1)
Platelets x103/µl 240 (200–400)

* Reference ranges are provided in parentheses

Figure 3—Histopathology of the thyroid gland in a Yorkshire Figure 4—Histopathology of the thyroid gland in a Yorkshire
terrier with hypothyroidism. Dilated follicles filled with colloid, terrier with hypothyroidism. Macrophages with amastigotes and
together with atrophic follicles, are evident (Hematoxylin and free parasitic forms are evident in the interstitium thicker spaces
eosin stain; 250X). (arrows) (Hematoxylin and eosin stain; 500X).

clustered around vessels or inside sinusoids [Figures 3, 4].
Histopathological examination of the skin biopsy showed
an increased thickness of the stratum corneum. The dermis
appeared thickened with swollen collagen fibers.
Macrophages rich in amastigotes and free parasitic forms,
together with some lymphocytes and plasma cells, were
present. Many hair follicles were in telogen arrest, with
follicular infundibula often dilated by keratin. Melanotic
debris and vacuolation of the arrector pili muscles were
also observed [Figures 5, 6].
A specific antiLeishmania treatment protocol was es-
tablished and included liposomal amphotericin B f
(3 mg/kg body weight, IV sid, for 10 consecutive days)
combined with supportive therapy (prednisone, 1 mg/kg
body weight, per os [PO] bid; lactated Ringer’s solution,
350 ml per day, IV). After one week’s treatment,
L-thyroxineg was administered at a dose of 20 µg/kg
body weight, PO, every 12 hours. After a slight initial
clinical improvement, the general condition of the dog
progressively deteriorated. Death, caused by myocardi-
490 JOURNAL of the American Animal Hospital Association November/December 1999, Vol. 35

Table 2
Results of Diagnostic Tests for Leishmaniasis (Serum Electrophoresis, Cytology, and Serology)
in a Four-Year-Old Yorkshire Terrier With Leishmaniasis and Hypothyroidism

Lymph Node and Bone Marrow

Electrophoretic Pattern* Parasitological Density
Total protein 7.0 g/dl (6.0–7.8) 6+ >100 amastigotes/microscopic field
Albumin 0.90 g/dl (2.3–3.4) 5+ 10–100 amastigotes/microscopic field†
α1 0.28 g/dl (0.20–0.50) 4+ 1–10 amastigotes/microscopic field
α2 0.53 g/dl (0.30–1.10) 3+ 1–10 amastigotes/10 microscopic fields
β1 0.44 g/dl (0.70–1.30) 2+ 1–10 amastigotes/100 microscopic fields
β2 0.86 g/dl (0.60–1.40) 1+ 1–10 amastigotes/1,000 microscopic fields
γ 3.99 g/dl (0.90–2.20) 0+ 0 amastigote/1,000 microscopic fields
A/G ratio 0.14 (0.70–1.11)

IFAT titer‡

1/640 (<1/80)

* Reference ranges are provided in parentheses

†
Result for the dog in this case report
‡
Leishmania immunofluorescent antibody titer

fiber discontinuity, granular degeneration, and hyalino-

Table 3
Results of Thyroid Function Testing in a
Four-Year-Old Yorkshire Terrier
With Leishmaniasis and Hypothyroidism
sis were also noted [Figure 7]. In all the other organs
examined, amastigotes were observed either free or in-
side macrophages, without significant concurrent inflam-
matory changes.

Discussion
Normal Reference
Hormones* Values Range Many authors have reported the association of leishma-
niasis in dogs with other diseases, such as neoplasms
T4 (µg/dl) 0.4 1.6–3.4 (e.g., hemangiosarcoma, lymphoma, myeloma), infec-
T4 (µg/dl)† 1.0 >1.9 tions (e.g., ehrlichiosis, hepatozoonosis), and parasitic
TSH (ng/ml) 0.9 <0.3 diseases (e.g., sarcoptic and demodectic mange).7–10 In
the leishmaniotic dog, appearance of clinical signs is
* T4=Tetraiodothyronine; TSH=thyroid-stimulating associated with the development of a T helper cell-2
hormone
†
(Th2) response characterized by high serum antibody
Six hours after thyroid-stimulating hormone (TSH)
administration (0.1 U/kg) levels, anergic response to intradermal antigens, sup-
pressed lymphoproliferative response, and low produc-
tion of protective cytokines.11,12 The severe immune
suppression caused by the protozoan may predispose to
tis (subsequently demonstrated by histopathology), oc- the onset and development of either infectious or neo-
curred 30 days after the initiation of treatment. plastic conditions. The clinical case reviewed in this
Histopathology was performed on samples of thyroid, paper is the first report of an endocrine pathology, hy-
lungs, mediastinal and mesenteric lymph nodes, heart, pothyroidism, associated with leishmaniasis. The para-
liver, kidney, spleen, stomach, small and large intes- site invaded not only the thyroid gland but all the other
tines, pancreas, adrenal and pituitary glands, and brain organs examined. The diagnosis of primary hypothy-
obtained at postmortem. In the myocardium, foci of in- roidism was based on clinical signs, laboratory data (in-
terstitial infiltration characterized by plasma cells, to- cluding thyroid function testing), histopathological
gether with macrophages rich in amastigotes, were examination of the thyroid gland and skin, and thyroid
observed. In areas neighboring these foci, signs of scintigraphy. This data, in its entirety, allows the exclu-
November/December 1999, Vol. 35
Figure 5—Skin histopathology in a Yorkshire terrier with hypo-
thyroidism. Increased thickness of stratum corneum is evident.
Vacuolated arrector pili muscles and swollen collagen fibers are
observed in the dermis (Hematoxylin and eosin stain; 200X).
Figure 6—Skin histopathology in a Yorkshire terrier with
hypothyroidism. Macrophages rich in amastigotes (arrows) are
evident between vacuolated arrector pili muscles (Hematoxylin
and eosin stain; 400X).
sion of euthyroid sick syndrome, which is also possible
in severe, chronic illnesses like leishmaniasis. It is diffi-
cult, however, in this case to determine whether and to
what extent the presence of amastigotes affected the
functional state of the thyroid (i.e., whether leishmania-
sis was the primary cause of glandular disease or whether
it only aggravated a pre-existing condition). In trypano-
somal infections in ruminants, decreased plasma levels
of thyroid hormones are coupled with structural damage
of the thyroid gland itself.2 Various pathophysiological
mechanisms resulting in glandular impairment have been
described by different authors, which can be directly and
indirectly ascribed to the presence of trypanosomes.3,4
The first is the release of biologically active factors (i.e.,
phospholipase, protease) capable of degrading protein
hormones, among which is thyrotropin release factor
(TRH).13 The indirect effects could be accounted for by
the establishment of a condition of chronic hypothalamic
Leishmaniasis in a Dog 491
Figure 7—Histopathology of the myocardium in a Yorkshire
terrier with hypothyroidism. Plasmacellular accumulations and
macrophages rich in amastigotes infiltrating the myocardial fibers
are seen. Signs of myofiber hyalinosis are evident (Hematoxylin
and eosin stain; 400X).
stress, with a consequent increase in corticosteroid lev-
els and a subsequent depressed activity of several pitu-
itary hormones and of thyroid function.4 Other authors
have hypothesized that the activation of the immune
system in protozoal infections causes the release of sev-
eral cytokines, among which is TNF-α, which may down-
regulate the endocrine system. Tumor necrosis factor-α
is capable of inhibiting the secretion of pituitary hor-
mones, such as gonadotropic hormone14 and TSH.15 In
this case, the authors found a marked rise in TNF-α
which may have had a pathophysiological role in the
hormonal imbalance. The ability of the Leishmania spp.
to cause the release of proteolytic factors that may affect
endocrine balance, could also be an important factor in
disease expression. In the future, growing interest in this
zoonotic disease should clarify the complex and the still
unknown relationship existing between leishmaniasis and
endocrine dysfunction in the dog.
a
Schirmer tear test; Schering-Plough Animal Health, Kenilworth, NJ
b
T4 RIA/Coated Tubes; Radim, Milano, Italy
c
Thytropar; Rorer, WA
d
Milenia Canine TSH; EIMA, Diagnostic Product Corporation,
Los Angeles, CA
e
Standard TNF-α used was a recombinant human TNF-α preparation;
Department of Immunology, Faculty of Veterinary Medicine, Utrecht,
the Netherlands
f
AmBisome; Vestar, San Dimas, CA
g
Eutirox; Bracco, Milano, Italy
Acknowledgments
The authors would like to thank Professor Francesco
Lamagna, Istituto di Clinica Chirurgica Veterinaria,
Università degli Studi di Napoli “Federico II,” for per-
forming the thyroid biopsy; Dr. Antonio Tommaselli,
Dipartimento di Endocrinologia ed Oncologia Clinica,
Facoltà di Medicina e Chirurgia, for performing the thy-
492 JOURNAL of the American Animal Hospital Association
roid scintigraphy; and Dr. Wilbert Bernardina, Depart-
ment of Immunology, Faculty of Veterinary Medicine of
Utretch, for the TNF-α assay. The assistance of Profes-
sor J. Verstegen, Service d’obstétrique et des troubles de
la roproduction des petits animaux, Universitè de Liège,
in conducting the TSH assay is also appreciated.
References
1. Hawking F, Greenfield J. Two autopsies of Rhodesian sleeping sickness:
visceral lesions and significance of changes in cerebrospinal fluid.
Trans R Soc Trop Med Hyg 1941;35:155–64.
2. Ikede BO, Logos GJ. Pathogenesis of Trypanosoma brucei infection in
sheep. III Hypophysial and other endocrine lesions. J Comp Path
1975;85:37–44.
3. Mutayoba BM, Gombe S, Kaaya GP, Waindi EN. Effect of chronic
experimental Trypanosoma congolense infection in the ovaries, pituitary,
thyroid and adrenal glands in female goats. Res Vet Sci 1988;44:140–6.
4. Mutayoba BM, Gombe S. Effect of African trypanosomias on plasma
cortisol and thyroxine concentration in goats. Res Vet Sci 1989;47:315–8.
5. Oliva G, Gradoni L, Cortese L, Orsini S. Comparative efficacy of
meglumine antimonate and aminosidine sulphate, alone or in combination,
in canine leishmaniasis. Annals Trop Med Parasitol 1998;92:165–71.
6. Hall IA, Campbell KL, Chambers MD, Davis CN. Effects of trimethoprim/
sulfamethoxazole on thyroid function in dogs with pyoderma.
J Am Vet Med Assoc 1993;202:1959–62.
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7. Margarito JM, Ginel PJ, Molleda JM, et al. Hemangiosarcoma associated
with leishmaniasis in three dogs. Vet Rec 1994;15:66–7.
8. Braca G, Macrì B, Galofaro V. Leishmaniosi e neoplasmi. Correlazioni ed
interferenze tra leucemia linfoide e leishmaniosi in un cane boxer di anni 7.
Riv Zoot Vet 1982;10:396–400.
9. Macrì B, GalofaroV, Braca G. Leishmaniosi e neoplasmi. Nota II:
correlazioni ed interferenze tra leishmaniosi e tumore venereo trasmissibile
(sarcoma di Sticker) nel cane. Atti Soc Ital Sci Vet 1982;36:510–2.
10. Ciaramella P, Oliva G, De Luna R, et al. A retrospective clinical study of
canine leishmaniasis in 150 dogs naturally infected by Leishmania
infantum. Vet Rec 1997;141:539–43.
11. Pinelli E, Killick-Kendrick R, Wagenaar J, Bernadina W, Del Real G,
Ruitenberg J. Cellular and humoral immune responses in dogs experimen-
tally and naturally infected with Leishmania infantum. Infect Immun
1994;62:229–35.
12. Martinez-Moreno A, Moreno T, Martinez-Moreno FJ, Acosta I, Hernandez
S. Humoral and cell-mediated immunity in natural and experimental canine
leishmaniasis. Vet Immunol Immunopathol 1995;48:209–20.
13. Tetaert D, Soudan B, Huet-Duvillier G, et al. Unusual cleavage of peptidic
hormones generated by tripanosome enzymes released in infested rat
serum. Int J Pep Protein Res 1993;2:147–52.
14. Walton PE, Cronin MJ. Tumor necrosis factor inhibits growth hormone
secretion from cultured anterior pituitary cells. Endocrinology
1989;125:925–9.
15. Pang XP, Hershman JM, Mirell CJ, Pekary AE. Impairment of hypotha-
lamic-pituitary-thyroid function in rats treated with human recombinant
tumor necrosis factor (cachectin). Endocrinology 1989;125:76–84.
 Suspected Myelinolysis Following Rapid
Correction of Hyponatremia in a Dog
A dog developed signs of neurological dysfunction five days after rapid correction of severe
electrolyte derangements, including hyponatremia, caused by gastrointestinal parasitism
(i.e., trichuriasis). History, laboratory findings, and onset of neurological signs following
correction of hyponatremia led to a diagnosis of myelinolysis. Myelinolysis is a
noninflammatory, demyelinating brain disease caused by sudden, upward osmotic shifts in
central nervous system plasma, often a result of rapid correction of chronic hyponatremia. The
pathogenesis is complex, but recovery is possible. Iatrogenic damage due to myelinolysis can
be avoided by adherence to therapeutic guidelines for correction of chronic hyponatremia.
J Am Anim Hosp Assoc 1999;35:493–7.

Richard K. Churcher, BVSc Introduction

A.D.J. Watson, BVSc, PhD, FRCVS
Andrew Eaton, BVSc
C concentration by more than 10 mEq/L per day, can cause symmetrical,
From the Department of Veterinary Clinical
Sciences (Churcher, Watson),
The University of Sydney,
New South Wales 2006, Australia, and
Kingsford Veterinary Hospital (Eaton),
70 Gardiner’s Road,
Kingsford, New South Wales 2032,
Australia.
Doctor Churcher’s current address is
North Shore Veterinary Hospital,
94 Alexander Street,
Crows Nest, New South Wales 2065,
Australia.
Myelinolysis is an iatrogenic brain disease, frequently reported in hu-
mans, caused in most instances by rapid correction of chronic hyponatre-
mia.1,2 Typically, the disease is seen in human alcoholics, liver transplant
recipients, and patients taking diuretics, many of who have a tendency to
develop electrolyte derangements.3 Rapid correction of chronic hyponatre-
mia with intravenous (IV) saline infusion, increasing plasma sodium
noninflammatory demyelination of stereotypical locations in the brain
including the pons, cerebellum, thalamus, external capsule, and basal
nuclei. Neuronal cell bodies and axons are generally spared.1 Sudden
osmotic gradients, created between replenished extracellular fluid (ECF)
and central nervous system (CNS) cells depleted of organic solutes (i.e.,
osmolytes), cause damage to myelin sheaths and the oligodendrocytes
which produce them.4 Signs of neurological dysfunction usually occur
several days after correction of hyponatremia and are typically motor and
localizing, in contrast to the diffuse encephalopathy of untreated chronic
hyponatremia. Death, permanent neurological impairment, and full re-
covery have all been reported.5 Myelinolysis has been produced experi-
mentally in several species, including dog, rat, and rabbit.1,2,6,7 Two cases
of naturally occurring canine myelinolysis have been reported; diagnosis
was made antemortem by magnetic resonance imaging (MRI) and was
confirmed by necropsy in one.8
This article reports a dog with gastrointestinal tract dysfunction and
electrolyte derangements associated with trichuriasis, in which severe
neurological signs, consistent with myelinolysis, developed several days
after rapid correction of chronic hyponatremia. Although gastrointestinal
signs resolved quickly following fluid and anthelmintic therapy, neuro-
logical signs required several weeks to dissipate.
Case Report
A six-year-old, 19.6-kg, neutered female Samoyed cross was presented to
Kingsford Veterinary Hospital with a history of diarrhea and weight loss
of six weeks duration, culminating in lethargy, inappetence, and vomit-
ing. Physical examination revealed a thin dog, 5% to 7% dehydrated,
profoundly weak, and unable to walk. Rectal temperature was 101˚ F, and

JOURNAL of the American Animal Hospital Association 493

494 JOURNAL of the American Animal Hospital Association
the heart rate was 120 beats per minute (bpm). Labora-
tory examination revealed neutrophilia (17.4 x109/L; ref-
erence range, 4.1 to 9.4 x109/L), lymphocytosis (3.7
x109/L; reference range, 0.9 to 3.6 x109/L), hyponatre-
mia (108 mEq/L; reference range, 130 to 153 mEq/L),
hyperkalemia (6.0 mEq/L; reference range, 3.9 to 5.7
mEq/L), and hypochloremia (77 mEq/L; reference range,
101 to 114 mEq/L). Mild hypoproteinemia was present
(5.3 g/dl; reference range, 5.5 to 8.0 g/dl) with an el-
evated blood urea nitrogen ([BUN], 33.6 mg/dl; refer-
ence range, 7.0 to 26.6 mg/dl) and poorly concentrated
urine (urine specific gravity [USG], 1.020). Remaining
hematological indices and serum biochemical values
were within reference ranges.
Fecal flotation revealed many Trichuris vulpis
(T. vulpis) eggs. A diagnosis of parasitic gastroenteritis
with secondary hypoadrenocorticism-like electrolyte de-
rangements was made, and the dog was placed on IV
lactated Ringer’s solution at a rate of 5 ml/kg per hour
with oral administration of a combination of praziquantel,
oxantel, and pyrantela and milbemycin oxime.b Fluids
were changed to 0.9% sodium chloride, and biochemical
tests nine hours later revealed plasma concentrations of
sodium at 125 mEq/L, potassium at 4.5 mEq/L, and
chloride at 95 mEq/L. Oral fenbendazolec was started at
50 mg/kg per day for three days. By the end of day three,
the dog seemed bright and alert and was eating and
walking, although still a little weak. At time of dis-
charge, plasma sodium concentration was 137 mEq/L,
potassium was 2.6 mEq/L, and chloride was 104 mEq/L.
Over the next three days, the dog continued to eat and
drink but became progressively weaker and more lethar-
gic. When reexamined, the dog was unable to walk, was
tachypneic, and was 10% dehydrated. Melena and
hematochezia were noted. Heart rate was 90 bpm, and
the rectal temperature was 100.7˚ F. Neurological ex-
amination revealed tetraparesis, dysphagia, and dimin-
ished bilateral menace response. Further IV fluid therapy
(i.e., lactated Ringer’s solution) was administered over
three days, but the dog’s neurological status continued to
deteriorate, and she was referred for further assessment.
Clinical examination at Sydney University Veteri-
nary Teaching Hospital (SUVTH) revealed a thin,
obtunded dog in lateral recumbency and unable to stand.
The dog was tachypneic and when stimulated would
spasmodically contract her thoracic limbs and exhibit
mild myoclonus, at which time she appeared agitated
and distressed. Rectal temperature was 98.7˚ F, heart and
pulse rates were 80 bpm, and capillary refill time (CRT)
was one second. Trismus was present, although the jaws
could be opened forcibly. Prehension of food appeared
difficult. When food and water were offered, exagger-
ated licking movements occurred and the dog weaved its
head about as if unable to locate the bowl. Once food
was in the mouth, swallowing appeared normal.
November/December 1999, Vol. 35
Neurological examination revealed absent bilateral
menace responses with normal pupillary light and
oculocephalic reflexes. A gag reflex was present. The
dog was tetraparetic and, although difficult to assess,
proprioception and postural reactions were absent. Mild
hyperreflexia of patellar and flexor reflexes was present,
and crossed extensor reflexes were inconsistently elic-
ited in both pelvic and thoracic limbs.
Hematology revealed a packed cell volume (PCV) of
35% (reference range, 37% to 55%), 2% reticulocytes
(reference range, 0% to 1.5%), mild anisocytosis and
eosinopenia (0; reference range, 0.14 to 1.2 x109/L), and
lymphopenia (0.2 x10 9/L; reference range, 0.9 to
3.6 x109/L). Abnormal biochemical findings were hy-
poalbuminemia (2.14 g/dl; reference range, 2.3 to 4.3
g/dl) and hypernatremia (156 mEq/L; reference range,
130 to 153 mEq/L). Urinalysis revealed dilute urine
(USG, 1.015). Electrocardiography was unremarkable.
Cerebrospinal fluid (CSF) collection, done under gen-
eral anesthesia, and analysis revealed a total protein of 8
mg/dl (reference range, 0 to 30 mg/dl), with three nucle-
ated cells per µl (reference range, less than five nucle-
ated cells per µl) consisting of lymphocytes, neutrophils,
and occasional monocytes and erythrocytes (1,034 per
µl; reference range, 0 to 30 erythrocytes per µl), which
was interpreted as likely blood contamination. An
adrenocorticotropic hormone (ACTH; acthargel at 2.2
mg/kg body weight, intramuscularly [IM]) response test
revealed a resting cortisol concentration of 59 nmol/L
(reference range, 25 to 75 nmol/L) with a two-hour post-
stimulation cortisol concentration of 887 nmol/L (refer-
ence range, 200 to 400 nmol/L). Basal ACTH was 144
ng/L (reference range, 30 to 80 ng/L).
Over the next two days, the dog ate and drank well
with assistance, was unable to stand, and did not def-
ecate. No medication was administered and fluid therapy
was discontinued. By day three, she was able to stand
and walk two or three paces with assistance, and vision
seemed normal. Semiformed feces were passed, which
tested negative for nematode ova, Giardia spp., and
blood. A rectal scraping was negative for Prototheca
spp. By day five, the dog appeared bright and alert, and
strength and locomotion were much improved. Gait ab-
normalities included pelvic and thoracic limb ataxia and
marked hypermetria. Postural reactions were sluggish.
Proprioception was present but diminished in pelvic
limbs and absent in thoracic limbs. Trismus had re-
solved, and the menace response was present bilaterally.
Liquid diarrhea was passed in association with tenes-
mus, increased defecation frequency, and mucus. A com-
bination of praziquantel, febantel, and pyrantela was
administered, and the following day the dog passed a
normal stool.
A presumptive diagnosis of myelinolysis secondary
to rapid correction of chronic hyponatremia was made,
and the dog was discharged from the hospital on day
November/December 1999, Vol. 35
eight, at which time thoracic limb gait appeared mildly
hypermetric with moderate proprioceptive deficits.
Monthly anthelmintic treatment (i.e., praziquantel,
febantel, and pyrantel a) was prescribed. On physical
examination one month later, the dog appeared clinically
normal.
Discussion
Myelinolysis as a cause of CNS dysfunction has been
recognized in humans since 1959.1 With the advent of
advanced imaging techniques such as computed tomog-
raphy (CT) and MRI, many reports of the condition have
emerged worldwide. Lesions were originally thought to
be confined to the pons, but are now regularly reported
in humans in extra-pontine locations such as the thalamus,
midbrain, cerebellum, basal nuclei, and cerebrocortical
grey and white matter junctions.5,9–11 Lesions produced
experimentally in dogs follow similar anatomic distribu-
tion, although thalamic lesions typically predominate.1,8
Two dogs reported previously with clinical signs of my-
elinolysis were found by MRI to have bilaterally sym-
metrical lesions within the central thalamus. 8 Much
speculation exists as to why lesions are distributed
stereotypically in the brain. One hypothesis suggests
predisposition for regions where extensive apposition of
vascular-rich grey matter and white matter occurs.12 Oth-
ers implicate oligodendrocyte topography13 and regional
concentrations of organic osmolytes14 as contributing
factors.
Myelinolysis is caused by rapid increases in CNS
plasma osmotic pressure. This is seen most commonly
following aggressive fluid therapy with sodium-rich flu-
ids for hyponatremia that has been present for more than
a few days; however, oral fluid restriction and isotonic
saline infusions can create similar lesions if plasma so-
dium concentrations rise rapidly as a consequence.1 Other
hyperosmolar solutions (e.g., mannitol) that perfuse
poorly into cells have reproduced myelinolysis experi-
mentally after rapid infusion.15 Experiments in rats sug-
gest that reinduction of hyponatremia following onset of
myelinolysis may aid recovery.16 Recommended rates of
correction of hyponatremia in humans aim to increase
plasma sodium concentration by no greater than 10
mEq/L per 24 hours.3 Similar recommendations have
been made for dogs.8,17 Fluid therapy in the present case
resulted in elevation of plasma sodium concentration by
17 mEq/L in nine hours, clearly exceeding current guide-
lines. The situation is somewhat different where hy-
ponatremia has been present less than 24 hours; in this
instance, cerebral edema secondary to acute-onset hy-
ponatremia can itself cause life-threatening, diffuse en-
cephalopathy and may warrant more aggressive fluid
therapy.17,18
The pathogenesis of myelinolysis is still unclear. Brain
electrolytes and other solutes play a key role in protect-
ing CNS cells from damage due to osmotic gradients
Myelinolysis in a Dog 495
created between ECF and the extracellular compartment.
With the onset of hyponatremia, sodium, potassium, and
chloride rapidly exit the cell, followed by other solutes
known as organic osmolytes. This group includes the
amino acids glutamine, glutamate, and taurine, as well as
myoinositol, phosphocreatine, and glycerophosphor-
ylcholine (GPC).7 As a result of this adaptive solute
translocation, equilibration of the osmotic gradient be-
tween ECF and the intracellular compartment occurs
within two to three days. After an initial influx of water
down the osmotic gradient, brain water levels return to
normal.3 With rapid correction of chronic hyponatremia,
CNS cells are now vulnerable to osmotic stress as blood
becomes hypertonic relative to the brain. Rapid compen-
satory intracellular influx of electrolytes and GPC oc-
curs, but reaccumulation of other organic osmolytes is
outpaced by rising plasma osmolality.7 This is particu-
larly true in certain regions of the brain where topo-
graphic correlation between demyelinating lesions and
delayed accumulation of osmolytes exists.14 The subse-
quent sequence of events is uncertain. Logically, one
would expect dehydration of brain cells, and this has
been demonstrated by some.7,19 However, others have
found increased brain water content after correction,
with electron microscopic studies revealing transient
breakdown of the blood-brain barrier due to endothelial
cell shrinkage, leakage of edema fluid perivascularly
(i.e., vasogenic edema), and subsequent degeneration of
myelin sheaths and oligodendrocytes. A direct toxic ef-
fect of sodium chloride-rich edema fluid on oligoden-
drocytes has been hypothesized in this setting.4,6
Clinical signs in the patient of this study closely re-
semble those in two confirmed canine cases of myelinoly-
sis, both of which had thalamic lesions.8 Obtundation,
quadriparesis, ataxia, hypermetria, loss of postural reac-
tions, upper motor neuron signs in limbs, episodic myo-
clonus or flexor spasms following stimulation, impaired
vision, trismus, and exaggerated licking were similarly
reported.8 Thalamic and subcortical white-matter lesions
could account for many of these signs.20
Laboratory findings supported the original diagnosis
of trichuriasis-associated hyponatremia and hyperkale-
mia. Eosinopenia with lymphopenia suggested cortisol
secretion, confirmed by hormone analyses. The high
basal ACTH concentration and supranormal increase in
cortisol on stimulation with ACTH were consistent with
pituitary-dependent hyperadrenocorticism, due either to
a stress-induced, physiological response or to an ACTH-
secreting pituitary tumor. The former seemed more likely
as severe, concurrent, systemic disease was present and
previous clinical history did not include signs sugges-
tive of pathological cortisol excess. Low urine concen-
tration in the presence of severe dehydration suggested
impaired renal concentrating ability secondary to renal
medullary solute depletion. Anemia and hypoalbumin-
emia could indicate recent gastrointestinal blood loss or
chronic inflammatory gastrointestinal disease.
496 JOURNAL of the American Animal Hospital Association
In humans with myelinolysis, CSF protein levels are
consistently increased, with myelin-basic protein (a by-
product of myelin degradation) present.5 The dog of this
study was not tested for the latter, and CSF protein levels
were normal, as in the two previously reported canine
cases. 8
Although later fecal flotations were consistently nega-
tive for T. vulpis, the large-bowel diarrhea on day four
was thought to be due to ongoing gastrointestinal para-
sitism, as whipworm egg burdens sometimes correlate
poorly with clinical infection.
Differential diagnoses for the neurological signs ex-
hibited by this dog include inflammatory encephalopa-
thies, intracranial vascular derangements, intoxication,
traumatic events such as tentorial herniation, and other
metabolic diseases.21 Normal CSF protein content and
absence of pleocytosis did not support an inflammatory
cause. Melena and hematochezia noted by the referring
veterinarian suggested the possibility of a hemostatic
defect; however, platelet numbers were normal. As bleed-
ing tendencies were not detected at SUVTH, intrinsic
and extrinsic coagulation pathways were not assessed.
Ischemic myelopathy secondary to thromboembolism
should result in increased CSF protein content secondary
to parenchymal necrosis.22 There was no history of expo-
sure to toxins, and laboratory findings did not support a
diagnosis of other metabolic diseases such as hypoglyce-
mia or hepatic encephalopathy. Increase in intracranial
volume due to edema can potentially exceed compensa-
tory limits, with resultant precipitous increase in intra-
cranial pressure leading to shifts in brain parenchyma.
Tentorial herniation often causes pressure on underlying
structures such as the brain stem, in particular the mid-
brain. 23 Oculomotor nerve dysfunction is common in
this setting; however, there was no evidence of this in the
patient of this study.
Definitive diagnosis of myelinolysis is made histo-
pathologically or by demonstration with brain imaging
techniques of symmetrical lesions in typical locations.
These are best seen using MRI and are typically
nonenhancing, hyperintense T2-weighted images.3,10
Neither procedure was performed in this case as the dog
was improving clinically three days after admission.
Thus, the diagnosis of myelinolysis is presumptive. How-
ever, the occurrence of typical signs five days after rapid
correction of a likely long-standing hyponatremia, and
their subsequent resolution, point strongly to myelinoly-
sis as the cause of the neurological dysfunction.
All canine cases of myelinolysis reported thus far
have been associated with T. vulpis infestation.8 While
trichuriasis-induced hyponatremia is documented,24,25 other
causes of hyponatremia, such as hypoadrenocorticism, ap-
pear to be more common in dogs.26–29 Curiously, signs of
myelinolysis have not been documented in any of these
animals, although many would have received similar
fluid therapy. Differences in the pathogenesis of hyponatre-
November/December 1999, Vol. 35
mia may play a role. Dogs with hypoadrenocorticism
hypersecrete corticotropin-releasing factor (CRF) in re-
sponse to hypocortisolemia. Antidiuretic hormone (ADH)
is cosecreted with CRF from paraventricular neurons, pro-
moting dilutional hyponatremia in addition to that caused
by renal sodium losses due to hypoaldosteronism.30 By
contrast, trichuriasis-associated hyponatremia is thought
to occur from direct gastrointestinal loss of sodium.24,25
In this setting, a large increase in plasma sodium concen-
tration may be more rapidly attainable during therapy
than in a dog with hypoadrenocorticism, where the
dilutional effects of ADH excess will tend to attenuate
increasing plasma sodium concentration following elec-
trolyte therapy.
Clinical presentations of posttherapy myelinolysis are
apparently rare in small animal practice. However, the
risk of myelinolysis occurring should always be consid-
ered when IV fluid therapy is undertaken in patients with
chronic hyponatremia. When hyponatremia is an inci-
dental finding and signs of cerebral edema (e.g., leth-
argy, nausea, vomiting, seizures, coma) are absent,
conservative therapy with mild water restriction and
monitoring of plasma sodium content can be imple-
mented. In patients with chronic hyponatremia and
plasma sodium concentrations less than 110 mEq/L, so-
dium (Na) deficit can be calculated using the formula:
Na deficit in mEq/L = 0.6 x lean body weight in kg x
(normal Na – patient’s Na).17 Using 0.9% sodium chlo-
ride containing 150 mEq Na, the total volume of fluid
(TVF) required for correction can be calculated. An esti-
mate of the volume that can be administered per day is
then:
5-10 x TVF
(normal Na – patient’s Na)
where 5-10 represents the desired correction rate of 5 to
10 mEq/L per day.
It is prudent to monitor plasma or serum sodium
concentration during correction of chronic hyponatre-
mia, as calculated rates of correction may not correspond
to actual changes in the patient, and to limit increments
in plasma sodium concentration to no more than 10
mEq/L per 24 hours.
a
Drontal; Bayer Australia, NSW, Australia
b
Endovet; Novartis Australia, NSW, Australia
c
Panacur 25; Hoechst Australia, Vic, Australia
Acknowledgment
Thanks to Dr. Richard Malik for assistance with this
case.
References
1. Laureno R. Central pontine myelinolysis following rapid correction of
hyponatremia. Ann Neurol 1983;13:232–42.
2. Illowsky BP, Laureno R. Encephalopathy and myelinolysis after rapid
correction of hyponatremia. Brain 1987;110:855–67.
November/December 1999, Vol. 35
3. Laureno R, Illowsky Karp BP. Myelinolysis after correction of hyponatre-
mia. Ann Int Med 1997;126:57–62.
4. Rojiani AM, Cho E-S, Sharer L, Prineas JW. Electrolyte-induced
demyelination in rats. 2. Ultrastructural evolution. Acta Neuropathol
1994;88:293–9.
5. Illowsky Karp BP, Laureno R. Pontine and extrapontine myelinolysis: a
neurologic disorder following rapid correction of hyponatremia. Medicine
1993;72:359–73.
6. Rojiani AM, Prineas JW, Cho E-S. Electrolyte-induced demyelination in
rats. 1. Role of the blood-brain barrier and edema. Acta Neuropathol
1994;88:287–92.
7. Lien Y-HH, Shapiro JI, Chan L. Study of brain electrolytes and organic
osmolytes during correction of chronic hyponatremia. J Clin Invest
1991;88:303–9.
8. O’Brien DP, Kroll RA, Johnson GC, Covert SJ, Nelson MJ. Myelinolysis
after correction of hyponatremia in two dogs. J Vet Int Med 1994;8:40–8.
9. Gocht A, Colmant HJ. Central pontine and extrapontine myelinolysis: a
report of 58 cases. Clin Neuropathol 1987;6:262–70.
10. Schimrigk S, Amoiridis G. Extrapontine myelinolysis. J Neurol Neurosurg
Psychiatry 1996;61:250.
11. Ellis SJ. Extrapontine myelinolysis after correction of chronic hyponatre-
mia with isotonic saline. Br J Clin Pract 1995;49:49–50.
12. Norenberg MD. A hypothesis of osmotic endothelial injury. A pathogenetic
mechanism in central pontine myelinolysis. Arch Neurol 1983;40:66–9.
13. Riggs JE, Schochet SS. Osmotic stress, osmotic myelinolysis and
oligodendrocyte topography. Arch Pathol Lab Med 1989;113:1386–8.
14. Lien Y-HH. Role of organic osmolytes in myelinolysis. A topographic
study in rats after rapid correction of hyponatremia. J Clin Invest
1995;95:1579–86.
15. Soupart A, Penninckx R, Stenuit A, Prospert F, Decaux G. Mannitol
induced brain myelinolysis in hyponatremic rats without correction of the
serum sodium. J Am Soc Nephrol 1994;5:374.
16. Soupart A, Penninckx R, Stenuit A, Perier O, Decaux G. Reinduction of
hyponatremia improves survival in rats with myelinolysis-related
neurologic symptoms. J Neuropathol Exp Neurol 1996;55:594–601.
Myelinolysis in a Dog 497
17. O’Brien D. The CNS effects of sodium imbalances. Proc 10th ACVIM
Forum, 1992:741–4.
18. Abercrombie SA. Hyponatremia: dangers of treatment. J S C Med Assoc
1991;87:163–7.
19. Sterns RH, Thomas DJ, Herndon RM. Brain dehydration and neurologic
deterioration after rapid correction of hyponatremia. Kidney Int
1989;35:69–75.
20. de Lahunta A. Diencephalon. In: de Lahunta A, ed. Veterinary neuro-
anatomy and clinical neurology. Philadelphia: WB Saunders, 1983:344–51.
21. de Lahunta A. Small animal neurologic examination and index of diseases
of the central nervous system. In: de Lahunta A, ed. Veterinary neuro-
anatomy and clinical neurology. Philadelphia: WB Saunders, 1983:365–87.
22. de Lahunta A. Cerebrospinal fluid and hydrocephalus. In: de Lahunta A,
ed. Veterinary neuroanatomy and clinical neurology. Philadelphia: WB
Saunders, 1983:30–52.
23. Bagley RS. Intracranial pressure in dogs and cats. Comp Cont Ed Pract Vet
1996;18:605–20.
24. DiBartola SP, Johnson SE, Davenport DJ, Prueter JC, Chew DJ, Sherding
RG. Clinicopathologic findings resembling hypoadrenocorticism in dogs
with primary gastrointestinal disease. J Am Vet Med Assoc 1985;187:60–3.
25. Malik R, Hunt GB, Hinchliffe JM, Church DB. Severe whipworm infection
in the dog. J Sm Anim Pract 1990;31:185–8.
26. Willard MD, Schall WD, McGaw DE, et al. Canine hypoadrenocorticism:
report of 37 cases and review of 39 previously reported cases. J Am Vet
Med Assoc 1982;180:59–62.
27. Schaer M, Chen CL. A clinical survey of 48 dogs with adrenocortical
hypofunction. J Am Anim Hosp Assoc 1983;19:443–52.
28. Melian C, Peterson ME. Diagnosis and treatment of naturally occurring
hypoadrenocorticism in 42 dogs. J Sm Anim Pract 1996;37:268–75.
29. Kintzer PP, Peterson ME. Treatment and long-term follow-up of 205 dogs
with hypoadrenocorticism. J Vet Int Med 1997;11:43–9.
30. Rose BD. Antidiuretic hormone and water balance. In: Rose BD, ed.
Clinical physiology of acid-base and electrolyte disorders. New York:
McGraw-Hill, 1994:155–64.
Regression of Hypertrophic Osteopathy in
a Cat After Surgical Excision of an
Adrenocortical Carcinoma
A 12-year-old, spayed, female domestic shorthair cat was diagnosed with severe and extensive
hypertrophic osteopathy of the appendicular skeleton. Diagnostic ultrasound detected a mass
lesion in the right adrenal gland. A right adrenalectomy was performed, and histopathological
examination confirmed an adrenocortical carcinoma. No radiographic evidence of pulmonary
metastasis was found on initial presentation or recheck thoracic radiographs taken 15 weeks
later. Almost complete regression of periosteal new bone formation occurred 15 weeks
following the successful surgical removal of the adrenal tumor.
J Am Anim Hosp Assoc 1999;35:499–505.

Timothy J. Becker, DVM, Introduction

Diplomate ACVIM
Ruby L. Perry, DVM,
Diplomate ACVR
G. L. Watson, DVM,
Diplomate ACVP
C usually occurs secondary to primary or metastatic pulmonary neoplasia
From the Internal Medicine Service (Becker)
and Radiology Service (Perry)
of the Department
of Small Animal Clinical Sciences,
and the Surgical Biopsy Service (Watson)
of the Animal Health Diagnostic Laboratory,
School of Veterinary Medicine,
Michigan State University,
East Lansing, Michigan 48824.
Doctor Becker’s current address is the
Veterinary Referral and Emergency Center,
123 West Cedar Street,
Norwalk, Connecticut 06854.
Hypertrophic osteopathy (HO) is a polyostotic bone disease characterized
by periosteal new bone formation. The periosteal new bone formation
usually occurs over the diaphyses of long bones and digits. The carpal and
tarsal bones can be involved, but to a lesser degree of severity. Radio-
graphically, the characteristic changes include a nodular, spiculated, or
palisade pattern of reactive periosteal new bone formation, leaving the
bones with an irregular surface. Hypertrophic osteopathy was referred to
as hypertrophic pulmonary osteoarthropathy in earlier literature and
in dogs.1–3 Less commonly, HO has been reported to occur secondary to
other intrathoracic diseases including pulmonary granulomatous disease,
pulmonary abscessation, intrathoracic esophageal granuloma due to Spi-
rocerca lupi, intrathoracic esophageal adenocarcinoma, and bacterial
endocarditis.1–7 Rarely, HO has been reported to be associated with intra-
abdominal neoplasia without intrathoracic involvement in the dog.1–3,8–11
Hypertrophic osteopathy has rarely been reported in cats.12–15 Hyper-
trophic osteopathy has also been reported in humans, horses, cattle, and
other species.1–3,16–20
The pathogenesis of HO is poorly understood. Increased circulation to
the extremities secondary to the underlying disease process is thought to
play a major role in the new bone formation in dogs and humans.16,21–22
Neurogenic and humorally mediated mechanisms have been proposed as
causes of the increased circulation to the extremities.23–26
To the authors’ knowledge, this is the first reported case of HO in a cat
secondary to an adrenal gland tumor, with regression of the skeletal
changes after successful surgical removal of the tumor. Long-term sur-
vival and the resolution of HO from a variety of other initiating causes
have been reported in humans, dogs, horses, and other species. 19,24,26–28
Case Report
A 12-year-old, 3.1-kg, spayed, female domestic shorthair cat was referred
to the Veterinary Teaching Hospital at Michigan State University (VTH-
MSU) with an 18-day history of decreased appetite, decreased activity,
and progressive lameness with swelling and pain in all four limbs. The

JOURNAL of the American Animal Hospital Association 499

500 JOURNAL of the American Animal Hospital Association
Figure 1A
Figures 1A, 1B—Lateral and craniocaudal radiographs of the
left front limb in a cat with hypertrophic osteopathy, demonstrat-
ing extensive periosteal new bone formation of a “palisade”
pattern involving the humerus, radius, and ulna (arrows).
cat’s condition had not been responsive to previous anti-
biotic therapy. The vaccination status of the cat was
current for rabies, rhinotracheitis, calici, and panleuko-
penia viruses. The referring veterinarian’s evaluation
one week prior to presentation included a normal com-
plete blood count (CBC), serum biochemical profile,
and urinalysis (UA). Serological tests for feline leukemia
virus (FeLV) and feline immunodeficiency virus (FIV)
were negative. Thoracic and abdominal radiographs were
unremarkable. Radiographs of the appendicular skeleton
demonstrated extensive periosteal reactions consistent with
hypertrophic osteopathy.
On presentation to the VTH-MSU, the cat was lethar-
gic and emaciated. The cat was reluctant to ambulate,
wobbly in gait, and had significant diaphyseal thicken-
ing in all four limbs. There appeared to be thickening of
both the long bones and the overlying soft tissue, but
pitting edema was absent. The limbs were also slightly
tender on palpation. Rectal body temperature was nor-
November/December 1999, Vol. 35
Figure 1B
mal. Cardiac auscultation detected a grade five out of six
systolic murmur that was loudest at the left parasternal
area of the thorax. The thyroid gland was normal on
palpation. The physical examination was otherwise un-
remarkable.
The minimum database collected included a CBC,
serum biochemical profile, UA, thyroid hormone profile,
and radiographs of the thorax and extremities. The CBC
was normal except for a mature neutrophilia (13.62 x103/
µl; reference range, 2.5 to 12.5 x103/µl). Abnormalities
on the serum biochemical profile included a low total
calcium (8.2 mg/dl; reference range, 8.4 to 11.5 mg/dl)
and an elevated alkaline phosphatase (105 IU/L; refer-
ence range, 4 to 81 IU/L). The UA was within reference
ranges. The thyroid hormone profile (i.e., total and free
tetraiodothyronine [T4] and triiodothyronine [T3]) was
normal.
Radiographs of the thorax, including left and right
lateral views and a ventrodorsal view, were unremark-
able. Radiographs of the limbs revealed extensive peri-
osteal new bone formation demonstrating a “palisade”
pattern involving the scapula, humerus, radius, ulna, dig-
its of the front limbs [Figure 1], and pelvis, femur, tibia,
November/December 1999, Vol. 35
Figure 2A
Figures 2A, 2B—Lateral and craniocaudal radiographs of the
right hind limb in a cat with hypertrophic osteopathy, demonstrat-
ing extensive periosteal new bone formation of a “palisade”
pattern involving the tibia, fibula, and tarsus (arrows).
fibula, tarsus, and digits of the hind limbs [Figure 2].
There was sparing of the carpus and the first digit in the
front limbs. Soft-tissue swelling was pronounced over
the distal femur, proximal tibia, distal humerus, and
proximal radius and ulna.
Since the thoracic radiographs did not demonstrate
signs of intrathoracic disease, an abdominal ultrasound
examination was performed to search for an intra-ab-
dominal cause of the HO. Diagnostic abdominal ultra-
sonography demonstrated a well-marginated hypoechoic
mass with mineralization between the caudate lobe of
the liver and the cranial pole of the right kidney in the
area of the right adrenal gland. The mass measured 2.1
by 1.1 cm [Figure 3]. The differential diagnoses for the
adrenal mass included adrenal gland hypertrophy, an
adrenocortical tumor, or a pheochromocytoma.
An ultrasound-guided fine-needle aspiration of the
mass was performed. Cytological examination demon-
strated a very cellular sample with large sheets of cohe-
Hypertrophic Osteopathy in a Cat 501
Figure 2B
sive cells [Figure 4]. These cells had abundant, foamy
cytoplasm with occasional multinucleated cells, a highly
variable nuclear to cytoplasmic ratio, anisokaryosis, and
a fine chromatin pattern. Nucleoli were prominent, vari-
able in size and number, and occasionally enlarged. The
cytological impression was a carcinoma, most likely of
endocrine origin.
To screen for a functional adrenocortical tumor, urine
was submitted for a cortisol:creatinine ratio, and plasma
was submitted for a resting cortisol concentration. The
urine cortisol:creatinine ratio was five (reference range
for this ratio is not well-defined in the cat; however,
there is evidence to suggest that reference ranges for the
cat are probably similar to those of the dog [canine
reference range at VTH-MSU, eight to 24]).29 The rest-
ing plasma cortisol concentration was normal (18
nmol/L; reference range, 15 to 97 nmol/L). These endo-
crine tests were not suggestive of active cortisol secre-
tion by the adrenal tumor.
In order to evaluate for intraocular signs of current or
previous systemic hypertension, a complete ophthalmic
examination was performed. Abnormalities on the oph-
thalmic examination were limited to the posterior seg-
502 JOURNAL of the American Animal Hospital Association
Figure 3—Diagnostic abdominal ultrasound image in the cat
from Figures 1 and 2, showing the well-marginated hypoechoic
mass between the caudate lobe of the liver and the cranial pole
of the right kidney in the area of the right adrenal gland. The
mass contained mineralization and measured 2.1 by 1.1 cm.
ment. Numerous, deep, intraretinal and choroidal hemor-
rhages were evident in the tapetal and nontapetal fundus.
Distinct alterations in the retinal vasculature included
numerous, focal constrictions of the retinal arterioles
resembling a “box-car” effect, and mild, focal widening
and compression of retinal venules at arteriovenous cross-
ings (“arteriovenous nicking”). Degeneration of the peri-
papillary retina in both eyes (OU) and peripapillary
exudate in the right eye (OD) was also evident. The
retinal hemorrhages and vascular changes were sugges-
tive of systemic hypertension. Other differentials for the
intraretinal hemorrhages included coagulopathies,
ehrlichiosis, and severe anemia. The hematocrit and
platelet counts were within reference ranges. A coagula-
tion profile and serology for Ehrlichia spp. were not
performed.
Indirect systolic Doppler blood pressure was mea-
sured from both the palmar metacarpal and plantar meta-
tarsal areas. Three consecutive systolic readings of 160
mmHg were obtained from both sites sampled (normal
value for cats at VTH-MSU is less than 160 mmHg
systolic). Diastolic blood pressure readings were not
obtained. Systolic blood pressure was rechecked several
times during the cat’s hospitalization period and was
found to range from 120 to 160 mmHg. Systemic sys-
tolic hypertension was ruled out on the basis of these
blood pressure readings.
An echocardiogram was performed to determine the
cause of the heart murmur. Mild left atrial enlargement
was noted. The echocardiogram was suggestive of mitral
regurgitation, but the heart rate was too rapid to clearly
document regurgitation with color-flow Doppler. Vigor-
ous left-ventricular wall and septal motion was detected;
however, left-ventricular wall thickness and septal thick-
November/December 1999, Vol. 35
Figure 4—Cytology of an ultrasound-guided fine-needle
aspirate of the adrenal mass from Figure 3. The cells had
abundant foamy cytoplasm with occasional multinucleated cells,
a highly variable nuclear to cytoplasmic ratio, anisokaryosis, and
a fine chromatin pattern. Nucleoli were prominent, variable in
size and number, and were occasionally enlarged (Hematoxylin
and eosin stain, 304X; bar=50 µm).
ness were within normal limits. There was no evidence
of hypertrophic cardiomyopathy nor vegetative lesions
on the aortic or mitral valves.
Surgery was performed to remove the affected adre-
nal gland. At surgery, the left adrenal gland was deter-
mined to be normal in size and shape. The right adrenal
gland was enlarged, the capsule was intact, and it was
not adhered to adjacent structures. A right adrenalec-
tomy was performed, and the tissues were submitted for
histopathological examination. The right adrenal gland
and the associated tumor weighed 3.8 grams and mea-
sured 25 mm in length, 19 mm in width, and 10 mm in
depth [Figure 5]. Additionally, bone biopsies were ob-
tained from the lateral surface of the proximal tibia and
submitted for histopathological examination. The cat re-
covered quickly and was discharged from the hospital
two days after surgery.
Histopathological findings of the bone biopsies dem-
onstrated multifocal necrotic foci and trabecular bone,
but were otherwise unremarkable. Histopathological ex-
amination of the right adrenal gland mass documented
the presence of an adrenocortical carcinoma. The carci-
noma had compressed the normal adrenal gland to a
minute rim of cortical and medullary cells and a rare
focus of cortical cells. There was relatively mild atypia,
with variability in nuclear size and in the nuclear to
cytoplasmic ratio, with occasional mitoses. The mass
was primarily expansile and was within the capsular
margins. Immunohistochemical staining of the adrenal
gland carcinoma was performed to determine the cell
origin. Staining was negative for the medullary markers
chromogranin A, neuron-specific enolase, and syn-
aptophysin, and was also negative for the cortical marker
cytokeratin. The immunohistochemical staining ruled out
a diagnosis of pheochromocytoma, as the results deter-
mined the tumor was not of medullary origin.
November/December 1999, Vol. 35
Figure 5—Photograph of the right adrenal gland cut in the
midsagittal plane, demonstrating the tumor. The right adrenal
gland with the tumor weighed 3.8 grams and measured 25 mm in
length, 19 mm in width, and 10 mm in depth.
Eight weeks postoperatively, the owner reported that
the cat was much more active, was jumping onto high
surfaces as it had in the past, and showed no evidence of
lameness or discomfort when running around the house.
On the follow-up physical examination, all four limbs
were normal on palpation. Follow-up radiographs of the
extremities were obtained [Figure 6]. There was a marked
change in the appearance of the bone formation. The
generalized periosteal bone formation was of a “lamel-
lar” pattern and smoothly marginated. There was no
evidence of reactive new bone growth.
On the 15-week postoperative recheck examination,
the owners reported that the cat was doing very well at
home and did not exhibit any abnormalities. There was
no evidence of pulmonary metastasis on thoracic radio-
graphs. Radiographs of the limbs demonstrated that the
remodeled “lamellar” periosteal pattern was less obvious
and remained smoothly marginated. An ophthalmologi-
cal recheck examination was performed, and the fun-
dic examination was normal. The intraretinal and
choroidal hemorrhages were resolved OU, and the
retinal vasculature appeared normal. The peripapil-
lary exudate OD had resolved.
Hypertrophic Osteopathy in a Cat 503
Discussion
Although numerous cases of HO have been reported in
dogs, only a few cases in the domestic cat have been
reported in the veterinary literature.1–3,13,16–18 In dogs,
the majority of HO cases occur in association with pri-
mary or metastatic pulmonary neoplasia. Rare cases of
HO in the dog have been associated with intra-abdomi-
nal neoplasia without pulmonary involvement.2,8–11 In
the few reported canine cases of HO with intra-abdomi-
nal neoplasia, none were associated with an adrenal tu-
mor.2,8–11
All four previously reported cases in domestic cats
were associated with neoplasia.12–15 Two of these were
associated with bronchiolar carcinoma; one was diag-
nosed with benign thymoma; and one was associated
with a renal papillary adenoma with no reported in-
trathoracic involvement.13,16–18 Three of the cats were
euthanized at the time of diagnosis, and the fourth cat
died during a radiographic procedure. The cat presented
in this paper was confirmed to have an adrenal gland
carcinoma with no apparent intrathoracic lesions. The
bony changes associated with HO progressively resolved
following surgical removal of the adrenal gland carci-
noma. There was no radiographic evidence of intratho-
racic metastasis on initial presentation and 15 weeks
postoperatively.
Adrenal cortical tumors can be highly aggressive and
may metastasize in spite of minimal cellular atypia.30,31
In this case, there was no evidence of pulmonary me-
tastases, intra-abdominal metastases on diagnostic
ultrasound, or gross metastases during abdominal ex-
ploratory surgery. At surgery, the capsule of the right
adrenal gland was still intact. There was concern regard-
ing the presurgical ultrasound-guided fine-needle aspi-
rate, in that it might increase the risk of spreading the
malignancy along the needle tract. Needle biopsy or
aspiration may not be recommended in cases where sur-
gical excision is contemplated, since the potential for
iatrogenic metastasis may exist. However, needle-tract
seeding with malignant cells is a rare complication fol-
lowing percutaneous fine-needle aspiration of abdomi-
nal tumors in human clinical case reports.32–34
The retinal changes were suggestive of current or
previous systemic hypertension; however, serial indirect
Doppler systolic blood pressure measurements were
within reference ranges. Indirect diastolic blood pressure
and direct arterial blood pressure were not measured.
The pathophysiology of HO is thought to result in part
from hyperperfusion of the appendicular tissues. Arterial
vasodilatation in the extremities could have resulted in
indirect blood pressure measurements that were not rep-
resentative of what was occurring systemically or dia-
stolic hypertension, but this is speculative. The retinal
hemorrhages and vascular changes had resolved by the
15th week postoperatively.
504 JOURNAL of the American Animal Hospital Association
Figure 6A
Figures 6A, 6B—Follow-up lateral radiographs of the extremities
in the cat from Figures 1 and 2 eight weeks postoperatively, which
were obtained to evaluate for regression of the periosteal new
bone formation. There was a marked change in the appearance of
the bone formation. The generalized periosteal bone formation
was of a “lamellar” pattern and smoothly marginated.
Since the retinal changes were suggestive of hyper-
tension, despite the normal indirect systolic blood pres-
sures, an evaluation for potential causes of systemic
hypertension was undertaken as part of the authors’ pre-
operative work-up. Differential diagnoses for systemic
hypertension include renal secondary hypertension, hy-
perthyroidism, hyperadrenocorticism, pheochromocy-
toma, and essential hypertension.
Renal values, urinalysis, and electrolyte concentra-
tions were normal. A presurgical thyroid hormone pro-
file was normal, and there was no palpable thyroid
nodule. The cat did not have the characteristic dermato-
logical findings of feline hyperadrenocorticism, and the
urine cortisol:creatinine ratio and resting plasma cortisol
concentration were not suggestive of hyperadrenocorti-
cism. Basal serum cortisol concentrations are not consid-
ered a valid screening test for hyperadrenocorticism since
serum cortisol concentrations vary considerably over
November/December 1999, Vol. 35
Figure 6B
time. Ideally, a low-dose dexamethasone suppression
test should have been performed preoperatively to screen
for hyperadrenocorticism.35 Intermittent hypertension
due to a pheochromocytoma was one distinct possibil-
ity.36 A 24-hour urine collection for catecholamines and
their metabolites was not performed. However, the corti-
cal location of the tumor, its histopathological appear-
ance, and special immunohistochemical stains for
specific biochemical markers ruled out a pheochro-
mocytoma. The initial retinal changes suggestive of hy-
pertension remain an enigma.
The referring veterinarian reported that the cat had the
systolic heart murmur prior to the current presenting
condition. There was no echocardiographic evidence of
cardiomyopathy or endocarditis. Bacterial endocarditis
is rarely reported in cats but has been reported to be
associated with HO and arterial hypertension in one
canine case.4,37–39 The HO in the cat reported here is
thought to be related to the adrenal tumor and not sec-
ondary to cardiac disease.
There are extensive and detailed discussions on the
proposed pathophysiology of HO reported in the veteri-
nary and human medical literature. Various mechanisms
November/December 1999, Vol. 35
have been proposed to attempt to explain how the pri-
mary lesions can mediate the skeletal changes observed
in HO. Neurogenic and humoral theories have been pro-
posed as possible explanations.23–26 The proposed neuro-
genic mechanism underlying hypertrophic osteopathy
suggests that a nervous reflex exists, with afferent fibers
originating in the thorax and efferent pathways affecting
the connective tissue and periosteum of the limbs.25
Production of a humoral or toxic factor from the
neoplastic cells leading to the HO seems a more plau-
sible explanation in cases of HO without intrathoracic
lesions. 24 The location of the tumor in the adrenal gland
cortex and the absence of pulmonary involvement in this
case raise the question of a possible humoral factor as an
inciting cause of the bony changes.
Serum and plasma samples were obtained prior to
surgery for future analysis for a possible humoral factor.
At the time of this publication, the authors have no
evidence that the tumor was actively secreting a humoral
factor.
References
1. Thrasher JP. Hypertrophic pulmonary osteoarthropathy in dogs. J Am Vet
Med Assoc 1961;139:441–8.
2. Brodey RS. Hypertrophic osteoarthropathy in the dog: a clinicopathologic
survey of 60 cases. J Am Vet Med Assoc 1971;159:1242–56.
3. Alexander JW. Hypertrophic osteoarthropathy in the dog. Canine Pract
1979;6:24–33.
4. Vulgamott JC, Clark RG. Arterial hypertension and hypertrophic
pulmonary osteopathy associated with aortic valvular endocarditis in a dog.
J Am Vet Med Assoc 1980;177:243–6.
5. Randolph JF, Center SA, Flanders JA, Diters RW. Hypertrophic osteopathy
associated with adenocarcinoma of the esophageal glands in a dog. J Am
Vet Med Assoc 1984;184:98–9.
6. Hasselink JW, van den Tweel JG. Hypertrophic osteopathy in a dog with a
chronic lung abscess. J Am Vet Med Assoc 1990;196:760–2.
7. Wylie KB, Lewis DD, Pechman RD, Cho DY. Hypertrophic osteopathy
associated with Mycobacterium fortuitum pneumonia in a dog. J Am Vet
Med Assoc 1993;202:1986–8.
8. Brodey RS, Riser WH, Allen H. Hypertrophic pulmonary osteoarthropathy
in a dog with carcinoma of the urinary bladder. J Am Vet Med Assoc
1973;162:474–8.
9. Halliwell WH, Ackerman N. Botryoid rhabdomyosarcoma of the urinary
bladder and hypertrophic osteoarthropathy in a young dog. J Am Vet Med
Assoc 1974;165:911–3.
10. Caywood DD, Osborne CA, Stevens JB, Jessen CR, O’Leary TP.
Hypertrophic osteoarthropathy associated with an atypical nephroblastoma
in a dog. J Am Anim Hosp Assoc 1980;16:855–65.
11. Rendano VT, Slauson DO. Hypertrophic osteopathy in a dog with prostatic
adenocarcinoma and without thoracic metastasis. J Am Anim Hosp Assoc
1982;18:905–9.
12. Carr SH. Secondary pulmonary osteoarthropathy in a cat. Feline Pract
1971;Nov/Dec:25–6.
13. Richards CD. Hypertrophic osteoarthropathy in a cat. Feline Pract
1977;Mar:41–2.
14. Roberg J. Hypertrophic pulmonary osteopathy. Feline Pract 1977;Nov/
Dec:18–22.
15. Nafe LH, Herron AJ, Burk RL. Hypertrophic osteopathy in a cat associated
with renal papillary adenoma. J Am Anim Hosp Assoc 1981;17:659–62.
16. Ginsburg J. Observations on the peripheral circulation in hypertrophic
pulmonary osteopathy. Quart J Med 1958;107:335–52.
17. Merritt AM, Dodd DC, Reid CF, Boucher WB. Hypertrophic pulmonary
osteopathy in a steer. J Am Vet Med Assoc 1971;159:443–8.
Hypertrophic Osteopathy in a Cat 505
18. Van de Watering CC, Zwart P, Bakker J. Cavernous tuberculosis of the
lungs and secondary hypertrophic osteo-arthropathy in a Siberian tiger
(Panthera tigrus). J Sm Anim Pract 1972;13:321–7.
19. Chaffin MK, Ruoff WW, Schmitz DG, Carter GK, Morris EL, Steyn P.
Regression of hypertrophic osteopathy in a filly following successful
management of an intrathoracic abscess. Equine Vet J 1990;22(1):62–5.
20. Lavoie JP, Carlson GP, George L. Hypertrophic osteopathy in three horses
and a pony. J Am Vet Med Assoc 1992;12:1900–4.
21. Holling HE, Brodey RS, Boland HC. Pulmonary hypertrophic osteoar-
thropathy. Lancet 1961;2:1269–74.
22. Holling HE, Danielson GK, Hamilton RW, et al. Hypertrophic pulmonary
osteoarthropathy. J Thorac Cardiovasc Surg 1963;46:310–21.
23. Steiner H, Dahlback O, Waldenstrom J. Ectopic growth hormone
production and osteoarthropathy in carcinoma of the bronchus. Lancet
1968;Apr 13:783–5.
24. Greenberg PB, Beck C, Martin TJ, Burger HG. Synthesis and release of
human growth hormone from lung carcinoma in cell culture. Lancet
1972;Feb 12:350–2.
25. Watson ADJ, Porges WL. Regression of hypertrophic osteopathy in a dog
following unilateral intrathoracic vagotomy. Vet Rec 1973;Sept:240–3.
26. Hara Y, Tagawa M, Ejima H, et al. Regression of hypertrophic osteopathy
following removal of intrathoracic neoplasia derived from vagus nerve in a
dog. J Vet Med Sci 1995;57(1):133–5.
27. Madewell BR, Nyland TG, Weigel JE. Regression of hypertrophic
osteopathy following pneumonectomy in a dog. J Am Vet Med Assoc
1978;172:818–21.
28. Kelly MJ. Long-term survival of a case of hypertrophic osteopathy with
regression of bony changes. J Am Anim Hosp Assoc 1984;20:439–44.
29. Goossens MM, Meyer HP, Voorhout G, Sprang EP. Urinary excretion of
glucocorticoids in the diagnosis of hyperadrenocorticism in cats. Domst
Anim Endocrinol 1995 Oct;12(4):355–62.
30. Myers III NC. Adrenal incidentalomas: diagnostic work-up of the
incidentally discovered adrenal mass. Vet Clin N Am Sm Anim Pract 1997
Mar;27(2):381–99.
31. Duesberg C, Peterson ME. Adrenal disorders in cats. Vet Clin N Am Sm
Anim Pract 1997 Mar;27(2):321–47.
32. Bergenfeld M, Genell S, Lindholm K, Ekberg O, Aspelin P. Needle tract
seeding after percutaneous fine-needle biopsy of pancreatic carcinoma.
Acta Chir Scand 1988 Jan;154(1):77–9.
33. Fornari F, Civardi G, Cavanna L, et al. Complications of ultrasonically
guided fine-needle abdominal biopsy. Results of a multicenter Italian study
and review of the literature. The cooperative Italian study group. Scand J
Gastroenterol 1989;24(8):949–55.
34. Voravud N, Shin DM, Dekmezian RH, Dimery I, Lee JS, Hong WK.
Implantation metastasis of carcinoma after percutaneous fine needle
aspiration biopsy. Chest 1992 Jul;102(1):313–5.
35. Smith MC, Feldman EC. Plasma endogenous ACTH concentrations and
plasma cortisol responses to synthetic ACTH and dexamethasone sodium
phosphate in healthy cats. Am J Vet Res 1987 Dec;48(12):1719–24.
36. Maher ER, McNeil EA. Pheochromocytoma in dogs and cats. Vet Clin N
Am Sm Anim Pract 1997 Mar;27(2):359–80.
37. Shouse CL, Meier H. Acute vegetative endocarditis of the aortic valve in
the dog and cat. J Am Vet Med Assoc 1956;129:278–89.
38. Yamaguchi RA, Pipers FS, Gamble DA. Echocardiographic evaluation of a
cat with bacterial vegetative endocarditis. J Am Vet Med Assoc 1983 Jul
1;183(1):118–20.
39. Thomas WP. Update: infective endocarditis. In: Bonagura JM, ed. Kirk’s
current veterinary therapy XI small animal practice. Philadelphia: WB
Saunders, 1992:752–5.
 Invasive Multiple Lymphangiomas
in a Young Dog
An unusual case of multiple lymphangiomas with lymph node involvement is described. A
seven-month-old, spayed female golden retriever was presented with a myriad of cystic
masses in the inguinal and caudal mammary regions. She was diagnosed with congenital
lymphangiomas (i.e., lymphatic hamartomas). As in human lymphangiomas, lymphatic
endothelial cells expressing factor VIII-related antigen and smooth muscle were present in this
case. A literature search did not identify similar characteristics in other reported canine
lymphangiomas. The dog was treated surgically and had a recurrence. Following a second
surgical intervention, she is now disease-free. J Am Anim Hosp Assoc 1999;35:507–9.

Marie C. Belanger, DMV Case Report

Igor Mikaelian, DMV
Christiane Girard, DMV, MSc,
Diplomate ACVP
Sylvie Daminet, DMV, MSc,
Diplomate ACVIM
C yielded the same cytological results. The animal was reexamined one
From the Departments of Clinical Studies
(Belanger) and Veterinary Pathology
(Mikaelian, Girard),
Faculté de Médecine Vétérinaire,
Université de Montréal,
C.P. 5000, St-Hyacinthe,
Quebec, Canada J2S 7C6
and the Department of Small Animal
Medicine and Surgery (Daminet),
The Royal Veterinary College,
Hawkshead Lane, North Mymms,
Hatfield, Herts, England AL9 7TA.
A seven-month-old, female spayed golden retriever was referred to the
Veterinary Teaching Hospital of the University of Montreal (VTHUM)
with a four-month history of subcutaneous (SC) turgid cystic masses
involving the inguinal and caudal mammary regions. The referring veteri-
narian had first seen this animal at 10 weeks of age for a 1 by 1-cm mass
in the right inguinal region. A fine-needle aspirate of the mass was
consistent with a hematoma. The entire content of the mass was emptied,
and no further investigation was performed. Over a one-month period, the
mass progressively recurred. Fine-needle aspirates were repeated and
month later. The inguinal mass was still present, but a distinct new mass
had appeared on the medial aspect of the left hind limb. No further
investigation was performed at that time. Two months later, the animal
was admitted for sterilization. The veterinarian found a myriad of nodules
(0.2 by 0.2 cm) along the left-caudal mammary chain. A clear fluid
obtained by fine-needle aspiration was submitted for cytological analysis
and interpreted as a transudate. The animal was then referred to the
VTHUM.
Upon presentation, the dog’s overall physical condition was good
except for multiple, alopecic, fluctuant, poorly circumscribed SC masses
ranging from 0.5 to 3 cm in diameter in the inguinal and caudal mammary
regions. The cystic masses were connected in some areas by a palpable,
cord-like structure. A clear, serous fluid oozed upon digital pressure of
the masses. Mild, nonpainful swelling of the dermis and subcutis was
present around the masses. The skin overlying the masses was neither
erythematous nor pruritic. Upon abdominal palpation, a cord-like exten-
sion of one of the inguinal masses extended into the inguinal canal toward
the abdominal cavity. The right inguinal lymph node was mildly enlarged
and firm. The dog’s vaccination status was current.
Diagnostic tests included a complete blood count (CBC),a serum bio-
chemical profile,b modified Knott’s test, fecal parasitological examina-
tion, complete coagulation profile (i.e., buccal mucosal bleeding time,
activated partial thromboplastin time, prothrombin time), abdominal ul-
trasonography, thoracic radiography, fine-needle aspirates of the masses,
as well as skin and inguinal lymph node biopsies. Results of the CBC,
serum biochemistry, modified Knott’s test, fecal analysis, coagulation
profile, and chest radiographs were within reference ranges. The abdomi-

JOURNAL of the American Animal Hospital Association 507

508 JOURNAL of the American Animal Hospital Association
Figure 1—Lymphangioma from a seven-month-old golden
retriever. Neoplastic lymphatic vessels of irregular size and
shape are embedded in dense, collagenous matrix with
numerous smooth muscle fibers. A lymphoid aggregate bulges
into the vascular lumen (Hematoxylin and eosin stain;
bar=150 µm).
nal ultrasonogram indicated a tubular cystic extension of
one of the inguinal masses toward the abdominal cavity
and possibly through the inguinal canal. The abdominal
organs showed no abnormalities. Cytology of the fluid
retrieved via fine-needle aspiration was interpreted as a
transudate (protein, 2.4 g/dl; specific gravity, 1.018;
nucleated cells, 0.88 x109/L) with a predominance of
lymphocytes (61%) accompanied by a few eosinophils
(8%) and plasmocytes. A mild histiocytic response was
also present. The lymphocyte population was composed
of small lymphocytes, prolymphocytes, and a few lym-
phoblasts. Erythrocytes were observed in large amounts
in some samples.
Upon surgery, the masses were poorly delineated.
They consisted of a myriad of 0.5 to 3-cm diameter
cystic cavities filled with a clear, watery fluid. One of
these masses extended deep into the inguinal canal and
was surgically resected. The inguinal lymph node was
slightly enlarged and was wet on cross section. All cuta-
neous masses and the inguinal lymph node were com-
pletely resected.
Forty-eight hours after surgery, the skin oozed sero-
sanguineous fluid, and the entire surgical region became
severely edematous and bruised. Hydrotherapy and cage
rest were started. The animal recovered uneventfully and
was discharged five days later.
Six months later, four nodular masses, measuring 1 to
3 cm in diameter, rapidly developed in the inguinal re-
gion a few centimeters from the initial site of the lesions.
These masses were surgically removed. Histologically,
they were identical to those initially excised.
Several masses and the inguinal lymph node were
routinely processed for histopathology. Sections of these
tissues were immunostained with rabbit polyclonal
antifactor VIII-related antigen and antismooth muscle
November/December 1999, Vol. 35
actin antibodies using an avidin-biotin immunoperoxi-
dase complex technique. Histopathologically, these tu-
mors were well delineated from the normal surrounding
tissues but were unencapsulated. They consisted of large,
irregularly shaped anastomosing vascular channels lined
by a discrete endothelium and supported by a delicate
meshwork of mature fibrovascular tissue [Figure 1]. En-
dothelial cells showed no cellular atypia and stained
strongly positive for factor VIII-related antigen. A few
fusiform cells formed an incomplete ring around the
vascular structures. These cells stained positively for
smooth muscle actin and were interpreted as smooth
muscle fibers. Vascular spaces were filled with a pale
proteinaceous fluid containing rare lymphocytes. The
stroma was multifocally infiltrated by few lymphocytes
occasionally forming lymphoid aggregates which pro-
truded into the vascular spaces. The medullary sinuses of
the inguinal lymph node were moderately distended by a
proteinaceous fluid, and the walls of some of them con-
tained a few smooth muscle fibers. There was also a
moderate diffuse paracortical and cortical lymphoid hy-
perplasia.
A diagnosis of multiple lymphangioma with lymph
node involvement was made, based on the macroscopic
and microscopic findings.
Discussion
Lymphangiomas are rare congenital or developmental
anomalies of the lymphatic system and are regarded as
benign neoplasms, hamartomas, or lymphatic malforma-
tions.1 They are considered as having minimal potential
for metastasis and limited invasion of surrounding struc-
tures.1 Lymphangiomas have been described in rats, dogs,
cats, cows, horses, mules, and humans.2 Congenital lym-
phangiomas (i.e., hamartomas) develop when primitive
lymphatic sacs fail to establish venous communication,
leading to the formation of cystic masses. In humans,
most lymphangiomas are present at birth or are detected
within the first years of life.3 Skin and SC tissue are the
most commonly affected sites.4
In dogs, 56 case records of lymphangioma have been
documented from 23 North American colleges of veteri-
nary medicine over a 30-year period (1964 to 1993), which
accounted for 0.005% of all canine entries.5 Golden re-
trievers are overrepresented among affected purebred dogs.
There is no sex predilection.2,6–11 Age of onset varies from
five weeks to eight years. Sites recorded involve the skin,
urinary bladder, liver, mediastinum, lung, mesentery, kid-
ney, tongue, spleen, mouth, and nasopharynx.2,3,5,6,12,13
These lymphatic defects generally form large, fluctuant,
poorly circumscribed masses.8 The clinical signs appear
secondary to lymphatic obstruction, organ compression, or
local invasion of adjacent tissue. Final diagnosis relies
upon histopathological examination of the mass.
Upon histopathology, this tumor has to be differenti-
ated from a cavernous hemangioma which generally is a
November/December 1999, Vol. 35
dark-red, well-circumscribed tumor. Lymphangiomas
consist of blood-filled, angular, vascular spaces lined
by a discrete endothelium, and their walls are always
devoid of lymphoid aggregates.13,14 Characteristic fea-
tures of hemangioma were absent from the tumor of
this study. The presence of blood in the first aspirate
may have been iatrogenic and reflected the puncture
of a blood vessel.
As in human lymphangiomas, lymphatic endothelial
cells (which expressed factor VIII-related antigen) and
smooth muscle cells were present in this case.14,15 Smooth
muscle cells had not been described in other reported
canine lymphangiomas, and expression of factor VIII-
related antigen had not been tested in these tumors.2,6,7–11
In the present case, the tumor recurred six months
after surgery. Recurrence of lymphangioma has often
been attributed to incomplete surgical resection. Alter-
natively, the high recurrence rate of these lesions6,9,11
may provide evidence that lymphangiomas are not true
neoplasms, but instead are lymphatic malformations that
arise from a failure of connection between lymph vessels
and the lymphatic system.13 Therefore, after incomplete
surgical resection, the remaining unconnected and ab-
normal lymphatics may eventually cause a clinical
relapse. Radiation therapy might provide a useful alter-
native for treatment of nonresectable or recurring le-
sions. 7 The reason why radiation therapy is sometimes
effective on such benign tumors remains unknown.
However, it should be emphasized that in humans
there are cases of malignant transformation following
radiation of lymphangiomas. Additionally, diuretic
administration may help alleviate clinical signs 16 by
decreasing venous pressure and thereby improving
net fluid reabsorption from the interstitial space. Glu-
cocorticoids are usually not helpful in these cases
since inflammatory cells are not present upon histo-
pathological examination. Moreover, glucocorticoids
may be deleterious by causing water retention, thereby
worsening the lymphatic congestion and local edema
in severely affected areas.
Long-term prognosis of lymphangiomas in the dog is
not well-established and probably depends on the ability
for complete surgical excision. In humans, complete sur-
gical excision is curative. 4
Conclusion
This is an unusual case of multiple lymphangiomas with
lymph node involvement in a young dog. Histopatho-
logical examination of the masses was required for diag-
nosis. As previously reported, canine lymphangiomas
characteristically have a prolonged course of disease
prior to histopathological diagnosis.8 As seen in this
case, diagnostic delay allows further tumor develop-
ment, making complete surgical excision difficult. Fur-
ther studies are needed to better characterize these rare
tumors in dogs.
Multiple Lymphangiomas in a Dog 509
a
Hematology analyzer; Cell-Dyn 3500, Abbott, Abbott Park, IL
b
Chemistry analyzer; Synchron cx-5, Beckman, Brea, CA
References
1. Wilcock BP. Neoplastic diseases of skin and mammary gland. In: Jubb
KVF, Kennedy PC, Palmer NC, eds. Pathology of domestic animals. 4th
ed. San Diego: Academic Press, 1993:727.
2. Remedios A, Bauer M, McMurphy R, Pharr J, Panciera D. Mediastinal
cystic lymphangioma in a dog. J Am Anim Hosp Assoc 1990;26:161–3.
3. Caro WA, Bronstein BR. Tumors of the skin. In: Moschella SL, Hurley JH,
eds. Dermatology. 3rd ed. Philadelphia: WB Saunders, 1985:1608–9.
4. Saijo M, Munroe IR, Mancer K. Lymphangioma: a long-term follow-up
study. Plast Reconstr Surg 1971;56:642–51.
5. Lawler DF, Evans RH. Multiple hepatic cavernous lymphangioma in an
aged male cat. J Comp Path 1993;109:83–7.
6. Stambaugh JE, Harvey CE, Goldschmidt MH. Lymphangioma in four dogs.
J Am Vet Med Assoc 1978;173:759–61.
7. Turrell JM, Lowenstine LS, Cowgill LD. Response to radiation therapy of
lymphangioma in a dog. J Am Vet Med Assoc 1988;193:1432–4.
8. Woods JP, Johnstone IB, Bienzle D, Gartley CJ. Concurrent lymphan-
gioma, immune-mediated thrombocytopenia, and von Willebrand’s disease
in a dog. J Am Anim Hosp Assoc 1995;31:70–6.
9. Fossum TW, Hodges CC, Scruggs DW, Fiske RA. Generalized
lymphangiectasis in a dog with subcutaneous chyle and lymphangioma.
J Am Vet Med Assoc 1990;197:231–6.
10. Post K, Clark EG, Gent IB. Cutaneous lymphangioma in a young dog.
Can Vet J 1991;32:747–8.
11. Berry WL, Nesbit JW, Pearson J. Lymphangiomatosis of the pelvic limb in
a maltese dog. J Sm Anim Pract 1996;37:340–3.
12. Padgett SL, Tillson DM, Henry CJ, Buss MS. Gingival vascular hamartoma
with associated paraneoplastic hyperglycemia in a kitten. J Am Vet Med
Assoc 1997;210:914–5.
13. Enzinger FM, Weiss SW. Tumors of lymph vessels. In: Enzinger FM,
Weiss SW, eds. Soft tissue tumors. 3rd ed. St. Louis: Mosby,
1994:679–700.
14. Walder EJ, Gross TL. Vascular tumors. In: Gross TL, Ihrke PS, Walder EJ,
eds. Veterinary dermatopathology. St. Louis: Mosby, 1992:419–29.
15. Nagle R, Witte M, Witte C, Way D. Factor VIII-associated antigen in
canine lymphatic endothelium. Lymphology 1985;18:84–5.
16. Scott DW, Miller WH, Griffin CE. Neoplastic and non-neoplastic tumors.
In: Scott DW, Miller WH, Griffin CE, eds. Small animal dermatology. 5th
ed. Philadelphia: WB Saunders, 1995:1045–6.
 Feline Retinal Degeneration: Clinical
Experience and New Findings (1994–1997)
A retrospective case series of 26 cats with diffuse retinal degeneration is presented. The most
common presenting complaints included bumping into objects, dilated pupils, and reluctance to
jump. Ophthalmic examination findings were consistent with those reported in dogs with
progressive retinal atrophy. Breed predilection of the Siamese cat was observed. Cats with
primary retinal degeneration presented late in the clinical course of their disease, when vision
loss was severe. Early symptoms such as night blindness and secondary ocular complications
(i.e., cataract and retinal detachment), reported in dogs with progressive retinal degeneration,
were not observed in this study. All cats showed excellent adaptive capabilities to blindness.
J Am Anim Hosp Assoc 1999;35:511–4.

Elizabeth A. Giuliano, DVM Introduction

Alexandra van der Woerdt, DVM,
MS, Diplomate ACVO
RS
Progressive retinal atrophy refers to a group of inherited retinal diseases
in dogs and cats.1 Progressive retinal atrophy is a bilateral, symmetrical,
progressive retinal degeneration resulting eventually in blindness. 2 Oph-
thalmic findings include mydriasis, weak to absent pupillary light re-
sponse, diffuse tapetal hyperreflectivity, retinal blood vessel attenuation,
optic nerve pallor, and impaired vision.2 Dogs with progressive retinal
atrophy may develop secondary ocular lesions such as cataract and retinal
detachment.1,3
Retinal degeneration in cats has not been studied as thoroughly as in
dogs. To date, research efforts have focused primarily on Abyssinian
cats.4–7 Studies of feline retinal degeneration in other breeds have been
rare and limited to select case reports in Persian, Siamese, and domestic
shorthair cats. 8–10
The objectives of this retrospective study were, first, to better describe
feline diffuse retinal degeneration and to determine if any age, sex, or
breed predilection existed in a random population of cats. Second, to
identify any potential risk factors in the progression of this disease,
including diet or drug therapy. Third, to evaluate if secondary intraocular
abnormalities develop in cats, as reported in dogs. Fourth, and finally, to
more formally examine the ability of cats to adapt to blindness through a
standardized interview process.

Materials and Methods

From the Department of Medicine,
the Animal Medical Center,
510 East 62nd Street,
New York, New York 10021.
Doctor Giuliano’s current address is the
Department of Veterinary Medicine
and Surgery,
College of Veterinary Medicine,
University of Missouri,
379 East Campus Drive,
Columbia, Missouri 65211.
All cats in which bilateral, generalized retinal degeneration was diag-
nosed between November 1994 and September 1997 at the Animal Medi-
cal Center and Ultravet Diagnostics were included in this study. Excluded
were cats with retinal degeneration secondary to glaucoma, any other
primary intraocular disease, or any systemic disease known to have
secondary ocular complications.
Medical records of 26 cats were reviewed, and the following informa-
tion was recorded: signalment, clinical signs on examination, vaccination
status, disease history, blood work (i.e., complete blood count, serum
biochemical profile, serum thyroxine concentrations), diagnostic proce-
dures, and medication history. Initial ophthalmic examination included
slit-lamp biomicroscopy and indirect ophthalmoscopy. Abnormalities on

JOURNAL of the American Animal Hospital Association 511

512 JOURNAL of the American Animal Hospital Association
ophthalmic examination suggestive of retinal degenera-
tion were tabulated to include the following: character of
the menace response (present, absent, or inconsistent);
character of the pupillary light response (present, absent,
or weak/inconsistent); degree of retinal vascular attenua-
tion (mild, moderate, severe); and degree of tapetal
hyperreflectivity (mild, moderate, severe). Intraocular
pressures were measured by applanation tonometry.a
Owners were contacted by telephone for an interview.
Owners were asked to review the initial clinical signs
that alerted them to an ocular or vision problem in their
cat and to assess the progression of vision loss (over
time). Owners were asked to give their cat’s dietary
history and comment on ocular or vision problems of any
known littermates. Owners were asked to describe their
cat’s quality of life as poor, fair, good, or excellent.
Disease and medication histories were reviewed with the
owner to confirm or further elucidate information from
the medical record.
Follow-up ophthalmic examinations were performed
to assess the occurrence of intraocular complications
secondary to retinal degeneration in a manner similar to
that of the initial ophthalmic examination: slit-lamp
biomicroscopy, indirect ophthalmoscopy, and applana-
tion tonometry in all cats. To minimize bias, the initial
ophthalmic examination findings were not reviewed by
the ophthalmologist before follow-up examination. Re-
sults of follow-up examinations were compared with the
results of each cat’s initial examination, and changes
were recorded.
A reference population for the breed and age distribu-
tions of these cats is not currently available, so statistical
analysis was not performed. The authors calculated mean,
median, and standard deviations of the data using statis-
tical software.b
Results
Diffuse retinal degeneration was diagnosed in 26 cats.
Breeds included the Siamese (n=11), domestic shorthair
(n=11), and one cat of each of the following breeds:
domestic longhair, Abyssinian, standard American short-
hair, and Maine coon. The mean age±standard deviation
(SD) of all the cats on initial examination was 9.5±4.7
years (median, 9.9 years). The mean age±SD of the
Siamese cats was 12.1±2.8 years, and that of all other
cats was 7.6±5.0 years. Fifteen cats were castrated males,
10 cats were spayed females, and one cat was an intact
female. All cats lived exclusively indoors.
Twenty cats were examined initially by the ophthal-
mology service, and six cats were referred to the oph-
thalmology service after consultation with internal
medicine specialists. Complaints on examination in-
cluded bumping into objects (n=17), dilated pupils (n=9),
and reluctance to jump (n=8). Other abnormalities noted
by the owners included reluctance to look up (n=3),
cloudy eyes (n=1), slow movement (n=1), and absent
November/December 1999, Vol. 35
menace response (n=1). Seven cats had no history of
vision loss. Four of these seven cats were perceived to
have vision loss by the admitting internal medicine clini-
cian and were subsequently referred to the ophthalmol-
ogy service for evaluation. Two of these seven cats were
presented to the ophthalmology service for evaluation of
dilated pupils, and one cat was referred for evaluation of
epiphora. Nineteen owners each reported that the abnor-
mal behavior exhibited by their cat had been slowly
progressive, with a mean time±SD of 4.0±4.9 months
(median, 2.3 months) from onset of clinical signs to
initial ophthalmic examination.
Abnormalities consistent with diffuse retinal degen-
eration found during ophthalmic examination of the 26
cats included absent menace response (n=17), weak men-
ace response (n=4), absent pupillary light response (n=4),
incomplete pupillary light response (n=12), and a large
resting pupil size (n=6). Optic nerve pallor was observed
in six cats. Twenty-two cats were judged to have severe
retinal vascular attenuation and severe diffuse tapetal
hyperreflectivity. Three cats had moderate retinal vascu-
lar attenuation and moderate diffuse tapetal hyper-
reflectivity. One cat had mild retinal vascular attenuation
and mild diffuse tapetal hyperreflectivity. Patchy depig-
mentation of the nontapetal area was noticed in one cat.
Other ophthalmic abnormalities observed included iris
atrophy in five cats, multiple pigmented spots in the iris
in one cat, and epiphora in one cat. Incipient anterior or
posterior cortical or lens suture cataract was noticed in
seven cats. Intraocular pressure was measured in two
cats and was within normal limits. Whole blood taurine
concentration was measured in one cat (369 nmol/ml;
reference range, 300 to 600 nmol/ml).
Vaccination status on examination was known in
19 cats and was up-to-date in 17 cats. Fifteen cats
were seronegative for feline leukemia virus (FeLV)
and feline immunodeficiency virus (FIV). Feline leu-
kemia virus and FIV status was unknown in 11 cats.
Sixteen cats including eight Siamese, six domestic
shorthair, one Abyssinian, and one Maine coon had
no previous medical problems before examination.
Ten cats (three Siamese and seven other cats) had
medical problems within 12 months before ophthalmic
examination. Lower urinary tract disease and inflam-
matory bowel disease were the most common prob-
lems reported. Medications administered within the
12-month period before examination included
enrofloxacin (for five cats), amoxicillin (for four
cats), and prednisone (for two cats).
Dietary information was obtained in 22 of 26 cats.
Sixteen cats were fed a variety of commercial diets;
five cats were fed prescription diets; and one cat was
fed a homemade diet. Information regarding family
members was obtained for three cats. Two siblings
and one parent were described by their owners as
having no perceived ocular or vision problems.
November/December 1999, Vol. 35
Of the owner population for the 26 cats, 19 were
contacted for a telephone interview at a mean±SD of
1.2±0.9 years (median, 1.1 years) after the initial exami-
nation was performed. Thirteen owners each judged their
cat’s quality of life (since the initial examination) to be
excellent, and six owners judged it to be good. Fourteen
owners each reported that their cat’s vision loss had been
stable since the initial examination, and five owners each
reported progression in their cat’s vision loss.
Seven of the 26 cats had follow-up ophthalmic exami-
nations. The second examination was conducted at a
mean±SD of 1.0±0.6 years (median, 0.8 years) after the
initial examination. Five of the seven cats had no clinical
differences between the first and second examinations.
One cat with a weak, inconsistent menace response and a
slow pupillary light response bilaterally on initial exami-
nation had progressed to a negative menace response and
a negative pupillary light response bilaterally on second
examination. One cat with normal lenses on initial ex-
amination had developed an incipient posterior cortical
cataract in the right eye and a prominent lens suture in
the left eye at follow-up examination. The intraocular
pressure was measured in both eyes by applanation
tonometry in all seven cats and found to be within nor-
mal limits. Retinal detachment was not observed on ini-
tial or follow-up ophthalmic examinations in any of the
cats.
Discussion
The breeds most commonly represented in the 26 cats
with retinal degeneration were the Siamese and the do-
mestic shorthair. The Siamese cats were older on exami-
nation than the other cats and had less variation in age
(mean±SD: Siamese, 12.1±2.8 years; all other cats, 7.6±5
years). There did not appear to be a sex predilection
among the cats in this study; only slightly more males
than females were presented.
Most cats had severe retinal changes at the time of
presentation to the ophthalmology service. The most
common complaints on ophthalmic examination were
bumping into objects, mydriasis, and reluctance to jump.
Although most owners had appreciated a slowly progres-
sive (over months) loss of vision in their cats, the vision
loss was most likely severe before owners were aware of
a problem. In the initial stages of progressive retinal
atrophy in the dog, decreased night vision is commonly
observed early in the disease process.1 This early clinical
sign was not observed by any cat owner in this study.
Ophthalmic findings were consistent with those pre-
viously reported in cats with retinal degeneration.9,11,12
All the cats in this study lived indoors and adapted well
to their blindness. All owners judged their respective
cat’s quality of life to be good to excellent. No owner
considered euthanizing his or her cat because of a known
handicap resulting from blindness. Further evidence of
good adaptation to blindness is the fact that seven own-
Feline Retinal Degeneration 513
ers did not appreciate loss of vision in their cats before
examination.
Causes of retinal degeneration include nutritional de-
ficiencies, 13 inflammatory diseases, 2,14 retinal detach-
ment with reattachment as seen in cats with systemic
hypertension, 15 and genetic abnormalities.7,8,10,11 All but
one cat in this study were fed commercial feline diets
from a variety of different pet food manufacturers, mak-
ing taurine deficiency unlikely. Plasma taurine concen-
tration was measured in one cat and was within reference
ranges.
Retinal degeneration secondary to inflammatory dis-
ease usually results in multifocal areas of retinal degen-
eration with possible involvement of the retinal pigmentary
epithelium and evidence of previous uveitis.16 All cats in
this study had diffuse, symmetrical, retinal degeneration
without evidence of previous or concurrent intraocular
inflammation. Approximately two-thirds of the cats had
no medical problems before retinal degeneration was
diagnosed. Half of these previously healthy cats were
Siamese. The remaining one-third of the population suf-
fered from a range of medical problems during the 12
months before examination, with the most common be-
ing lower urinary tract disease.
Systemic hypertension can lead to an acute retinal
detachment.15 Once hypertension is appropriately treated,
the retina may reattach, often resulting in diffuse retinal
degeneration. Blood pressures were not obtained in the
cats of this study. However, the slowly progressive onset
of vision loss in combination with the complete absence
of intraocular hemorrhage makes hypertension with reti-
nal detachment and subsequent reattachment unlikely in
these cats.
Retinal degeneration often occurs in uncontrolled
glaucoma.2 Although intraocular pressures were not mea-
sured consistently on initial ophthalmic examination,
other signs consistent with previous or concurrent glau-
coma (such as optic nerve cupping) were never observed
in any cat in this study, and no owner reported any
historical episode consistent with ocular pain or buph-
thalmia. Intraocular pressures were found to be within
normal limits in all cats on follow-up examination.
Adverse reactions to some medications include blind-
ness.17 A variety of medications were administered to
several of the study cats within the 12 months before
examination. Enrofloxacin was used most commonly.
Vision loss is not a reported side effect of this medica-
tion in cats. Studies of other fluoroquinolones in cats
have demonstrated electroretinographic changes and his-
topathological abnormalities in the rods and cones.18 At
this time, no information is available regarding the reti-
nal toxicity of enrofloxacin in the feline.
Early-onset rod-cone dysplasia has been described in
the Abyssinian,6 Persian,8 and mixed-breed cats.10 Al-
though modes of inheritance may differ, cats with early-
onset dysplasia show degenerative retinal changes within
514 JOURNAL of the American Animal Hospital Association
the first few months of life. In contrast, late-onset pro-
gressive retinal atrophy has been described in the Abys-
sinian cat.4,7 In this breed, ophthalmological changes can
first be observed between one and two years of age.
Affected cats progress to complete blindness by middle
age or older. A cause for the primary retinal degenera-
tion in the cats of this study could not be determined. The
Siamese cats were relatively homogeneous in age and
health status compared with the other cats. Previous
studies have suggested hereditary progressive retinal at-
rophy in Siamese cats.9,19 The other cats varied consider-
ably in age, disease, and medication history.
Dogs with progressive retinal atrophy can develop
secondary ocular lesions. Cataracts commonly develop
in poodles with progressive retinal atrophy and have
been reported in other breeds in the later stages of this
disease.1 In addition, a thin peripheral retina may tear
and result in a retinal detachment.1 Important ocular
complications secondary to retinal degeneration were
not present in cats in this study.
Conclusion
In this case series, a predilection for retinal degeneration
within Siamese cats was observed. No dietary or drug
factor was identified as contributing to the progression
of retinal degeneration in this population of cats. Cats
with primary retinal degeneration do not develop impor-
tant secondary ocular complications as seen in dogs,
according to the results of this study.
The authors recognize the inherent limitations in this
retrospective study, including the lack of a reference
population, initial examination of cases at near end-stage
progression of disease, and difficulty in securing a ma-
jority of follow-up examinations. The feline retinal de-
generation observed in this study was slowly progressive
in nature, as evidenced by historical findings and follow-
up information. The predilection for Siamese cats as
observed in this random population suggests that a he-
reditary form of progressive retinal atrophy may exist in
this breed. Early diagnosis may be missed due to excel-
lent feline adaptive capabilities, especially if housed ex-
clusively indoors. Progressive retinal degeneration in
cats is probably more common than is currently sup-
posed. The importance of routine funduscopic examina-
tions is emphasized to help in the identification and
study of this disease process. Further investigation of the
Siamese breed is needed to determine what mode of
inheritance, if any, exists for progressive retinal degen-
eration in this breed.
a
Tono-Pen XL Applanation Tonometer; Mentor O&O Inc., Norvell, MA
b
Excel 4.0 a; Microsoft Corp., Redmond, WA
November/December 1999, Vol. 35
References
1. Millichamp NJ. Retinal degeneration in the dog and cat. In: Millichamp NJ,
Dziezye J, eds. Vet Clin N Am Sm Anim Pract 1990;20:799–835.
2. Barnett KC, Curtis R, Millichamp NJ. The differential diagnosis of retinal
degeneration in the dog and cat. J Sm Anim Pract 1983;24:663–73.
3. Peiffer RL, Wilcock BP, Yin H. The pathogenesis and significance of pre-
iridal fibrovascular membrane in domestic animals. Vet Pathol
1990;27:41–5.
4. Narfstrom K. Progressive retinal atrophy in the Abyssinian cat: clinical
characteristics. Invest Ophthalmol Vis Sci 1985;26:193–200.
5. Narfstrom K, Nilsson SEG. Progressive retinal atrophy in the Abyssinian
cat: an update. Vet Rec 1983;112:525–7.
6. Barnett KC. Progressive retinal atrophy in the Abyssinian cat. J Sm Anim
Pract 1982;23:763–6.
7. Narfstrom K. Hereditary progressive retinal atrophy in the Abyssinian cat. J
Hered 1983;74:274–6.
8. Rubin LF, Lipton DE. Retinal degeneration in kittens. J Am Vet Med
Assoc 1973;162:467–9.
9. Carlile JL. Feline retinal atrophy. Vet Rec 1981;108:311.
10. West-Hyde L, Buyukmihci N. Photoreceptor degeneration in a family
of cats. J Am Vet Med Assoc 1982;181:243–7.
11. Barnett KC, Curtis R. Autosomal dominant progressive atrophy in
Abyssinian cats. J Hered 1985;76:168–70.
12. Carlile JL, Carrington SD, Bedford PGC. Six cases of progressive retinal
atrophy in Abyssinian cats. J Sm Anim Pract 1984;25:415–20.
13. Barnett KC, Burger IH. Taurine deficiency retinopathy in the cat. J Sm
Anim Pract 1980;21:521–34.
14. Davidson MG, Nasisse MP, English RV, Wilcock BP, Jamieson VE. Feline
anterior uveitis: a study of 53 cases. J Am Anim Hosp Assoc
1991;27:77–83.
15. Stiles J, Polzin DJ, Bistner SI. The prevalence of retinopathy in cats with
systemic hypertension and chronic renal failure or hyperthyroidism. J Am
Anim Hosp Assoc 1994;30:564–72.
16. Curtis R. Retinal diseases in the dog and cat: an overview and update. J Sm
Anim Pract 1988;29:397–415.
17. Imperia PS, Lazarus HM, Lass JH. Ocular complications of systemic
cancer chemotherapy. Surv Ophthalmol 1989;34:209–30.
18. Schluter G. Ciprofloxacin: review of potential toxicologic effects. Am J
Med 1987;82:91–3.
19. Barnett KC. Retinal atrophy. Vet Rec 1965;77:1543–52.
 A Two-Dimensional Analysis of
Limb Symmetry in the
Trot of Labrador Retrievers
Sixteen sound Labrador retriever and Labrador retriever cross-breed adult dogs were evaluated
for symmetry while in a trot gait using a two-dimensional motion analysis system. Reflective
markers were placed at selected joint centers. Each dog had the right side and then the left
side videotaped while in the trot gait. The markers on the videotape were then digitized for
analysis. There was no significant difference (p less than 0.05) between the movements of the
two sides. It was concluded that the trot gait is symmetrical and that a two-dimensional system
can be used to analyze gait in the dog. J Am Anim Hosp Assoc 1999;35:515–20.

Robert L. Gillette, DVM, MSE Introduction

Body movement can be used to evaluate the physical status of the subject
Carole J. Zebas, PED
in question. By understanding and defining normal movement, one can
then evaluate abnormal movement. Animal movement has been a subject
of research for a long time.1 Both qualitative and quantitative gait analy-
O ses have been used to analyze horse and dog movements.2,3 It has been
used to evaluate normal gaits (i.e., trot) and abnormal gaits in dogs with
hip dysplasia and cranial cruciate ligament rupture. 4–6 Limb symmetry
indices have been evaluated using ground reaction forces and kinemati-
cally to assess hind-limb symmetry. 7,8 Motion analysis can play a very
important role in helping to understand how the body is functioning.
Veterinarians, breeders, owners, and trainers can potentially benefit
from the recent advances in gait analysis. Improved capabilities for data
collection, storage, and analysis in combination with the advancements in
personal computer technology have provided an opportunity for these
analytical techniques to be utilized in the respective areas of interest.
Currently these capabilities are only accessible at the institutional level,
or they are so highly technical that its use is limited. The authors believe
that a priority should be placed on researching methodologies that provide
these tools to the professionals who can utilize them.
The objectives of this study were to kinematically describe the trot in
the Labrador retriever/Labrador cross-breed dog and to assess the limb
symmetry in the trot of the Labrador retriever using a two-dimensional
video analysis system.

Materials and Methods

From the Scott-Ritchey
Research Center (Gillette),
College of Veterinary Medicine,
Auburn University,
Auburn, Alabama 36849
and the
Department of Health, Sport, and
Exercise Science (Zebas),
University of Kansas,
Lawrence, Kansas 66045.
The study was conducted under protocols approved by the Auburn Uni-
versity Institutional Animal Care and Use Committee and the University
of Kansas Institutional Animal Care and Use Committee.
Animals
Sixteen clinically sound Labrador retriever and Labrador cross-breed
dogs that were older than two years of age and younger than eight years
participated in the study. Veterinary records for each participant were
examined for any historical orthopedic abnormalities. Soundness by ex-
amination was defined as a zero degree of lameness when using the
lameness quantification system described by Sumner-Smith.9

JOURNAL of the American Animal Hospital Association 515

516 JOURNAL of the American Animal Hospital Association November/December 1999, Vol. 35

Experimental Design parameters that did not have a significant difference

Reflective markers were made by cutting a 1-inch between the paired right and left sides were considered
symmetrical.
styrofoam balla in half. Retroreflective tapeb was placed on
the styrofoam to reflect light back to the camera. Reflec- Results
tive markers were placed at the joints of the defined body
For reliability, one dog was put through the methodology
segments. This was done by first placing masking tapec
three times. The coefficient of variance, significance
over the predefined locations. Adhesive glued was applied
level of p less than 0.10, was determined for the angular
to the back of the reflective markers, and then the markers
displacement of the shoulder, elbow, carpus, hip, stifle,
were attached to the tape at the anatomical points to be
and tarsus for both the right and left sides. The results are
measured. The axial markers were placed behind the ear on
reported in Table 1.
the lateral aspect of the atlantal vertebral bone, on the
The values from the right side were then compared to
dorsal aspect (i.e., point of cranial angle) of the scapula, on
the left side using a paired t-test statistical equation with
the dorsal point of the iliac crest, and on the lateral point of
a significance level of p less than 0.05. The means,
the ischial tuberosity. The forelimb appendicular markers
standard deviations, maximums, and minimums of the
were placed on the acromion/greater tubercle of the
linear kinematic parameters are shown in Table 2 and
scapulohumeral joint, on the lateral epicondyle of the hu-
summarized in Figure 1. The means, standard devia-
merus, on the ulnar styloid process/ulnar carpal bone of the
tions, maximums, and minimums of the angular kine-
carpus, and on the distal lateral aspect of the fifth metacar-
matic parameters are shown in Table 3 and summarized
pal bone. The hind-limb appendicular markers were placed
in Figure 2. The results of the t-test scores are listed in
on the eminence of the greater trochanter of the femur, on
Table 4. There was no significant difference between the
the femorotibial joint midpoint between the lateral epicon-
values derived for both the right and left sides.
dyle of the femur and the fibular head, on the lateral
prominence of the malleolus of the distal tibia, and on the Discussion
distal lateral aspect of the fifth metatarsus.
Body movement can be used to evaluate lameness and
The test area was a level and even roughened concrete
gait abnormalities in the dog. If normal movement were
surface. The camera was placed perpendicular to the move-
symmetrical between both sides of the body, then any
ment of the canine subject, 20 feet from the test subject
abnormal movement of a body segment would produce
path. The movement was filmed by an SVHS video cam-
asymmetrical locomotion. This plays an important role
erae at a speed of 60 Hz using a shutter speed of 1/500
in the evaluation of conformation, lameness, perfor-
seconds. A handler led the dogs on the test path at a speed
mance, and rehabilitation.
that induced a trot gait. The dogs were trotted on the test
The significance of the reliability showed that the
path first with their right side perpendicular to the camera
methodology used in this study was consistent and re-
and then with their left side perpendicular to the camera.
peatable. There was no significant difference between
This was repeated for three sequences.
the kinematic measurements of the right side and those
After filming, the videotape was subjected to a kine-
of the left side. Healthy, sound Labrador retrievers and
matic analysis using the Peak5 motion analysis software
Labrador retriever cross-breed dogs move symmetrically
package.f The reflective balls were used in locating the x
while in a trot gait.
and y coordinates for each of the joint centers.
Previous studies have established that computer-as-
Motion Evaluation sisted videographic gait analysis can be used to analyze
canine locomotion. These studies were performed using
The linear kinematic parameters measured were the stride
a three-dimensional motion analysis system. The aver-
length, stride frequency, stride time, and linear velocity.
age stride length for this study was longer, the average
The angular kinematic parameters were the angular dis-
stride frequency was faster, and the linear velocities
placement of the shoulder, elbow, carpal, hip, stifle, and
were faster than those reported in other studies.4,10 There
tarsal joints and the angular velocity of the shoulder and
was also an increase in the degrees of angular displace-
hip joints. A Butterworth filter, which is incorporated
ment in this study as compared to the other studies, as
within the Peak Performance analysis software,f was used
seen in Table 5. These somewhat higher values could be
on the kinematic data. The results of the three sequences
a result of the trotting pace differences in previous stud-
were then averaged for repeatability using a coefficient of
ies. Another reason for the higher values could be the
variance. After defining the linear kinematic parameters,
way the parameters were defined. The lack of a signifi-
the angular parameters of the right side were compared
cant difference between the kinematic measurements of
with those of the left side to assess symmetry.
the two sides shows that it is possible to use the two-
Statistical Analysis dimensional analysis system for determining gait sym-
Paired t-tests were used to determine if there was a metry. One previous study used a two-dimensional
significant difference between kinematic parameters. All system to characterize normal locomotion of the dog
November/December 1999, Vol. 35 Analysis of Limb Symmetry 517

Table 1
Reliability of the Digitizing Technique

Angular Displacement Measurements in One Dog

Repeating the Methodology Three Times
Joint Body Side Sequence 1 Sequence 2 Sequence 3 Co. Var.*
Shoulder Right 41.09 44.16 36.81 0.0907
Shoulder Left 41.59 38.65 39.14 0.0396
Elbow Right 69.60 67.68 61.15 0.0670
Elbow Left 65.56 71.96 65.64 0.0542
Carpus Right 143.88 142.26 153.26 0.0405
Carpus Left 148.96 156.31 145.78 0.0359
Hip Right 40.14 39.94 42.10 0.0293
Hip Left 47.03 46.45 39.74 0.0912
Stifle Right 76.58 69.99 70.39 0.0511
Stifle Left 60.85 65.75 57.19 0.0701
Tarsus Right 67.90 61.39 70.39 0.0932
Tarsus Left 66.46 54.89 58.18 0.0996

NOTE: The values for the measured angular displacements are in degrees
* Co. Var.=coefficient of variance values

Table 2
The Mean, Standard Deviation, Maximum, and Minimum Values
of the Linear Kinematic Parameters

Kinematic Parameter* Body Side Mean SD† Maximum Minimum

Stride length (m) Right 1.2139 0.1540 1.5125 1.0121
Stride length (m) Left 1.2214 0.1718 1.7077 1.0172
Stride time (s) Right 0.4259 0.0369 0.4843 0.3507
Stride time (s) Left 0.4330 0.0497 0.5177 0.3507
Linear velocity (m/s) Right 2.8721 0.4424 3.6228 2.0898
Linear velocity (m/s) Left 2.8581 0.5244 4.0903 1.9745
Stride frequency (str/s) Right 2.3650 0.2099 2.8514 2.0648
Stride frequency (str/s) Left 2.3370 0.2609 2.8514 1.9316

* m=meters; s=seconds; str=strides

†
SD=standard deviation

using nonlinear dynamic stability measurements.11 Us-
ing the protocol described in this current study, the move-
ments filmed on the right side can be compared to the
movements filmed on the left side. The two-dimensional
system can be used as an alternative to the three-dimen-
sional system to measure body symmetry.
Conclusions
There are two areas of conclusions as a result of this
study. The first is that there were no significant differ-
ences found between the right and left side parameters in
sound dogs. This gait symmetry has the potential to be
used diagnostically, in that a parameter on one side of
the body could be used as the control for the same
parameter on the opposite side. When assessing gait and
joint movement in the trot, any difference between the
two sides could be used to help diagnose lameness. Fur-
ther tests are needed to evaluate the use of this methodol-
ogy on unsound or lame subjects.
Second, the results also show that a two-dimensional
analysis system is both valid and reliable. It allows the
filming of one side of the body to be followed by filming
518 JOURNAL of the American Animal Hospital Association November/December 1999, Vol. 35

Table 3
The Mean, Standard Deviation, Maximum, and Minimum Values
of the Angular Kinematic Parameters

Kinematic Parameter* Body Side Mean SD† Maximum Minimum

Shoulder ROM (degs) Right 42.98 5.35 56.36 35.68
Shoulder ROM (degs) Left 42.60 6.80 58.16 33.52
Elbow ROM (degs) Right 69.09 10.64 94.84 52.48
Elbow ROM (degs) Left 66.08 5.38 79.04 57.55
Carpal ROM (degs) Right 150.02 14.51 179.66 135.61
Carpal ROM (degs) Left 143.88 9.85 165.79 124.31
Hip ROM (degs) Right 45.65 5.30 58.15 37.14
Hip ROM (degs) Left 43.36 9.21 66.76 28.37
Stifle ROM (degs) Right 65.86 8.98 79.93 48.49
Stifle ROM (degs) Left 65.97 11.64 96.07 48.92
Tarsus ROM (degs) Right 61.27 7.01 71.80 48.34
Tarsus ROM (degs) Left 59.10 8.14 76.21 45.46
Shoulder AV CW (degs/s) Right 378.86 84.99 612.30 287.10
Shoulder AV CW (degs/s) Left 355.94 59.02 468.40 260.30
Shoulder AV CCW (degs/s) Right 460.46 120.00 686.80 212.40
Shoulder AV CCW (degs/s) Left 416.78 97.87 586.90 251.50
Hip AV CW (degs/s) Right 251.63 65.61 397.10 167.60
Hip AV CW (degs/s) Left 290.09 74.18 406.90 172.10
Hip AV CCW (degs/s) Right 374.41 207.16 946.90 160.60
Hip AV CCW (degs/s) Left 333.21 151.07 698.80 154.60

* ROM=range of motion or angular displacement; degs=degrees of movement; AV=angular velocity; CW=clockwise

movement; s=seconds; CCW=counterclockwise movement
†
SD=standard deviation

Figure 1—A graph comparing the means of the linear kinematic
parameters of the right side to those of the left side from dogs
undergoing two-dimensional gait analysis. There was no
significant difference (p less than 0.05) in any of the parameters
compared [see Table 2].
Figure 2—A graph comparing the means of the angular
kinematic parameters of the right side to those of the left side
from dogs undergoing two-dimensional gait analysis. Measure-
ments are in degrees of range of motion. There was no signifi-
cant difference (p less than 0.05) in any of the parameters
compared [see Table 3].
November/December 1999, Vol. 35 Analysis of Limb Symmetry 519

Table 4
Results of the Statistical Analysis for the Comparison of Right and
Left Kinematic Parameters in the Assessment of Gait Symmetry

Kinematic Parameter* t-test Value Deg. of F.† P Value Significance

Stride length 0.217 15 0.831 NS‡
Stride time -0.752 15 0.464 NS
Linear velocity 0.543 15 0.595 NS
Stride frequency 0.629 15 0.539 NS
Shoulder ROM 0.284 15 0.781 NS
Elbow ROM 1.202 15 0.248 NS
Carpal ROM 1.842 15 0.085 NS
Hip ROM 0.875 15 0.395 NS
Stifle ROM -0.0415 15 0.967 NS
Tarsal ROM 0.998 15 0.334 NS
Shoulder CW AV 1.373 15 0.190 NS
Shoulder CCW AV -1.518 15 0.150 NS
Hip CW AV -1.488 15 0.158 NS
Hip CCW AV -0.586 15 0.567 NS

* ROM=range of motion or angular displacement; CW=clockwise movement; AV=angular velocity;

CCW=counterclockwise movement
†
Deg. of F.=degrees of freedom
‡
NS=nonsignificant

analysis system. Such individuals could send videotapes

Table 5 to the laboratories that have these systems for gait analy-
sis. Any individual that would learn the protocol could
Angular Displacement Values of Right-Side then benefit from computer-assisted video gait analysis.
Joints While in the Trot Compared to Future studies should include more information on
Previously Reported Right-Side Values the different breeds. This would help in defining the
conformation standards for breeding purposes. Analysis
Results of Allen, DeCamp, of more sound dogs in general would define the normal
Joint This Study et al.10 et al.4
maximum and minimum ranges. This would help when
Shoulder 43.0 29.4 30.3 diagnostically analyzing gait. Increasing the number of
Elbow 69.1 55.8 53.7 dogs analyzed that have prediagnosed musculoskeletal
Carpus 150.0 102.3 106.0 pathologies would set standards for the parameters that
Hip 45.6 30.4 31.0 are associated with those specific etiologies. Once some
Stifle 65.9 49.5 54.1 of these standards are set, this methodology can be used
Tarsus 61.3 48.7 37.0 to quantify response to treatment in a clinical setting or
in the research environment.
NOTE: The values for the measured angular displace- Professionals, trainers, and owners should be edu-
ments are in degrees cated on the use of computer-assisted video gait analy-
sis. The more information that is distributed, the greater
the potential to benefit from the knowledge gained about
of the opposite side of the body, with similar results. The animal locomotion.
two-dimensional analysis system is more economical
than the three-dimensional system, and because of this, it a
Floracraft, Ludington, MI
would be more affordable to those individuals that could b
3M Scotchlite retroreflective tape #7610; 3M, St. Louis, MO
utilize these methodologies. c
National Tape Corp., New Orleans, LA
A major benefit of the two-dimensional analysis sys-
tem is that filming outside of the laboratory is possible.
Not all clinicians have the potential to purchase a motion (Continued on next page)
520 JOURNAL of the American Animal Hospital Association November/December 1999, Vol. 35

d 4. DeCamp CE, Soutas-Little RW, Hauptman J, et al. Kinematic gait analysis

Livestock identification tag cement; W.J. Ruscoe Co., Akron, OH
e of the trot in healthy greyhounds. Am J Vet Res 1993;54:627–34.
Panasonic Systems Co., Secaucus, NJ
f 5.
Peak Performance Technologies, Inc., Englewood, CO
Acknowledgment
The authors would like to thank Dr. Paul Rumph for the
use of his laboratory and instrumentation.
References
1. Leach DH, Dagg AI. Evolution of equine locomotion research.
Equine Vet J 1983;15:87–92.
2. DeCamp CE. Kinetic and kinematic gait analysis and the assessment of
lameness in the dog. Vet Clin N Am (Sm Anim Pract) 1997;27:825–40.
3. Leach DH, Dagg AI. A review of research on equine locomotion and
biomechanics. Equine Vet J 1983;15:93–102.
Bennet RL, DeCamp CE, Flo GL, et al. Kinematic gait analysis in dogs
with hip dysplasia. Am J Vet Res 1996;57:966–71.
6. DeCamp CE, Riggs CM, Olivier NB, et al. Kinematic evaluation of gait in
dogs with cranial cruciate ligament rupture. Am J Vet Res 1996;57:120–6.
7. Budsberg SC, Jevens DJ, Brown J, et al. Evaluation of limb symmetry
indices, using ground reaction forces in healthy dogs. Am J Vet Res
1993;54:1569–74.
8. Schaefer SL, DeCamp CE, Hauptman JG, et al. Use of kinematic analysis
to evaluate hind-limb symmetry of the trot in healthy dogs. Vet Surg
1996;25:437.
9. Sumner-Smith G. Gait analysis and orthopedic examination. In:
Slatter DS, ed. Textbook of small animal surgery. 1993:1577–86.
10. Allen K, DeCamp CE, Braden TD, Bahns M. Kinematic gait analysis
of the trot in the healthy mixed breed dogs. Vet Comp Ortho Traum
1994;7:148–54.
11. Marghitu DB, Kincaid SA, Rumph PF. Nonlinear dynamics stability
measurements of locomotion in healthy greyhounds. Am J Vet Res
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 Surgical Treatment
of Idiopathic Pericardial Effusion in the
Dog: 25 Cases (1978–1993)
Twenty-five cases of canine idiopathic pericardial effusion are described. All were treated
surgically and underwent thoracotomy and pericardectomy, with histopathological evaluation of
the resected pericardial sac. No tumor, infection, granulation tissue, or foreign body was found.
Thirteen of the 25 dogs were golden retrievers, and all were large or giant breeds. Three (12%)
died in the immediate postoperative period, and four (16%) died within one year of signs
possibly related to the original condition. Eighteen (72%) survived at least 18 months; seven
died or were euthanized for reasons unrelated to pericardial effusion (median, 44 months); and
11 were still alive at last contact (median, 61 months). J Am Anim Hosp Assoc 1999;35:521–5.

Michael G. Aronsohn, VMD, Introduction

Diplomate ACVS Idiopathic pericardial effusion (IPE) is a condition in which serosan-
James L. Carpenter, DVM, guinous to bloody fluid accumulates in the pericardial sac and no evi-
Diplomate ACVP dence of neoplasia, cardiac disease, trauma, infection, or uremia can be
found.1–9 Idiopathic hemorrhagic pericardial effusion, idiopathic pericar-
dial hemorrhage, spontaneous pericardial effusion, benign idiopathic peri-
carditis, and benign pericardial effusion are terms that have, at times,
been applied to this condition in the dog. The specific etiology of IPE
RS remains unidentified, as historically all diagnostic tests (including radiog-
raphy, ultrasonography, electrocardiography, pneumopericardiography,
cytology, microbiology, and histopathology) have failed to demonstrate a
definitive cause.4,5,9–12 Surgical treatment by pericardectomy has been
reported for 23 of 38 cases previously described in the veterinary litera-
ture; however, satisfactory follow-up information on these cases is not
available.13–17
The purpose of this report is to describe the clinical and histopathologi-
cal features and outcome of 25 additional cases of IPE in dogs treated by
pericardectomy.

Materials and Methods

From the Departments of Surgery
(Aronsohn) and Pathology (Carpenter),
Angell Memorial Animal Hospital,
350 South Huntington Avenue,
Boston, Massachusetts 02130.
Doctor Aronsohn’s current address is
Veterinary Specialists of South Florida,
9410 Stirling Road,
Cooper City, Florida 33024.
Criteria for inclusion in this study included: 1) significant pericardial
effusion causing clinical signs; 2) thoracotomy with pericardectomy and
histopathological evaluation of resected pericardium; and 3) no evidence
of tumor, infection, granulation tissue, or foreign body.
The case records of all dogs with pericardial effusion presented to
Angell Memorial Animal Hospital between 1978 and 1993 were re-
viewed. Of the 81 dogs identified, 47 were eliminated on the basis of
disqualifying information in the patient record. Nine more cases were
eliminated by review of histopathology or by follow-up information
received from telephone interviews with referring veterinarians. The 25
dogs in this study were divided into three groups:
Group I: Nonsurvivors
Dogs that died before hospital discharge. All dogs in this group had a
necropsy.

JOURNAL of the American Animal Hospital Association 521

522 JOURNAL of the American Animal Hospital Association
Table
Causes of Death in Group III Dogs
Survival Time
Case/Breed (months)*
1. Golden retriever 18
2. Golden retriever 24
3. Golden retriever 36
4. Collie cross 48
5. Old English sheepdog 48
6. Golden retriever 60
7. Golden retriever 72
* Survival times are approximate in some cases and are based on owner or veterinarian recollection and not medical
records. Medical records of deceased patients are not retained at many hospitals.
Group II: Short-term Survivors
Dogs that died within one year after hospital discharge
of causes possibly related to the original disease process.
Group III: Long-term Survivors
Dogs that lived at least 18 months with no recurrence of
related clinical signs.
Thirteen dogs underwent a right lateral thoracotomy
through the fourth or fifth intercostal space, and 12 dogs
had a median sternotomy. From 1978 to 1982, single or
multiple openings were created ventral to the phrenic
nerve near the apex of the heart in four dogs to allow
continuous drainage of pericardial fluid into the thoracic
cavity (pericardiotomy). Subtotal pericardectomy was
done on all dogs after 1982 (in 21 cases). The pericardial
sac ventral to the phrenic nerves was resected through
either a lateral thoracotomy or median sternotomy inci-
sion. Nine different surgeons performed the 25
procedures. Pericardial tissue was submitted for histo-
pathological evaluation in all cases.
Results
Thirteen (52%) of the dogs in this study were golden
retrievers, and two (8%) were German shepherd dogs.
The remainder were individual purebred dogs or mixed
breeds. All dogs were relatively large, with a minimum
weight of 25 kg (55 lb). There were 10 neutered females,
10 intact males, and five neutered males. The male:female
ratio was 1.5:1. The median age was seven years, with a
range from three to 14 years. Ascites was noted as an
initial physical examination finding in 17 dogs (68%).
Group I: Nonsurvivors (12%)
Three dogs died in the intensive care unit during the
immediate postoperative period at one, three, and seven
days after surgery. In all cases, death was associated
with respiratory arrest. Autopsy revealed the cause of
November/December 1999, Vol. 35
Cause of Death
Malignant melanoma of digit; metastatic lung disease
Large abdominal mass; metastatic lung disease
Euthanasia; severe arthritis
Euthanasia; vestibular disease
Euthanasia; respiratory disease
Euthanasia; thoracic wall mass
Euthanasia; oral fibrosarcoma
death to be pulmonary thromboembolism in one dog and
myocardial necrosis in two dogs; however, the etiology
could not be determined. Both dogs with myocardial
necrosis had a significant amount of bloody fluid present
in the thoracic cavity.
Group II: Short-term Survivors (16%)
Four dogs lived between one and 12 months (median, 7.5
months) after pericardectomy and died of causes possi-
bly related to the original disease process. Circumstances
involving the death of each patient were established in
telephone conversations with the owner and/or referring
veterinarian. One dog developed acute respiratory dis-
tress and died within 24 hours at 12 months postopera-
tively. One dog recovered well for three weeks after
surgery and then rapidly declined and was euthanized. A
St. Bernard was euthanized after developing edema of all
four limbs 12 months postoperatively and being unable
to walk. Another dog was euthanized six months after
surgery for recurrent episodes of thoracic effusions that
required drainage. No necropsies were performed on
dogs in this group.
Group III: Long-term Survivors (72%)
The 18 dogs in this group were followed for at least 18
months and either died or were euthanized for reasons
unrelated to pericardial effusion (n=7), or they were still
alive at last contact (n=11). Dogs that died or were
euthanized had lived for 18 to 72 months (median, 44
months) after pericardectomy [see Table]. Last contact
with owners or veterinarians of surviving dogs was 20 to
96 months (median, 61 months) postoperatively.
Histopathological Findings
All 25 dogs had biopsy sections of their pericardial sac
examined histopathologically. The microscopic findings
of pericardial sacs with IPE consisted of diffuse fibrosis,
November/December 1999, Vol. 35
Figure 1—Photomicrograph of a normal fibrous pericardium
from a dog. The inner surface (top) is covered by a single, flat
layer of mesothelial cells. The fibrous portion overlies mediastinal
adipose tissue, with two veins and an arteriole shown (Hema-
toxylin and eosin stain, 52X).
congestion, old and recent foci of hemorrhage, few in-
flammatory cells, regions void of parietal mesothelium,
and areas of mesothelial hyperplasia [Figures 1, 2]. Some
sacs had distinct layers of fibrosis of variable matura-
tion, with the most immature layer (having fibrin depos-
its) located at the innermost portion in contact with the
effusion. The laminae of fibrosis suggest an episodic
effusive process.
Three of the 25 dogs had biopsy specimens of the
parietal portion of the sac that had “onion-skin” fibrosis
about blood vessels located within the fibrotic lamina.
Some vessels had been obliterated by thrombosis and
fibrosis, leaving only “onion-skin” fibrotic nodules [Fig-
ure 3]. None of the dogs included in this report had a
prominent leukocytic, plasma cell, or mast cell inflam-
matory component in their pericardium. Hemosiderin-
laden macrophages varied from few to many. The small
numbers of lymphocytes and plasma cells, when present,
were in a perivenous pattern.
Idiopathic Pericardial Effusion 523
Figure 2—Photomicrograph of the fibrous pericardium, from a
dog with idiopathic pericardial effusion, that is about three times
normal thickness. Mesothelial cells are absent. The dense zone
of regular fibrosis has larger and older vessels in its deeper zone
(Hematoxylin and eosin stain, 52X).
The mediastinal cardiac pleura that is continuous with
the fibrous layer of the sac usually had increased vascu-
larity and congestion, with or without perivascular lym-
phocytic nodules or fibrosis within the fat.
Discussion
The use of the term idiopathic pericardial effusion
throughout this paper reflects the preferred terminology
of the authors based on the clinical findings of this
condition. This is consistent with terminology used in a
recent study of dogs with pericardial effusion.18 The
terms idiopathic pericardial hemorrhage and idiopathic
hemorrhagic pericardial effusion, as used in previous
reports in the veterinary literature, can be used inter-
changeably with IPE. 13–17
The total number of dogs reported with IPE in previ-
ous studies was 38.13–17 Pericardectomy was performed
in 23 of these cases; seven were managed by pericardio-
centesis alone; and eight were euthanized. Most dogs
524 JOURNAL of the American Animal Hospital Association
Figure 3—Photomicrograph of a thickened and nodular fibrous
pericardium from a dog with idiopathic pericardial effusion. The
nodularity is caused by chronic thrombosis and perivascular
fibrosis (Hematoxylin and eosin stain, 52X).
were reported to be of large or giant breeds. There were
six St. Bernards, five Great Danes, and five golden re-
trievers, as well as one miniature schnauzer14 and one
miniature poodle.15 In one study involving 10 dogs, in-
formation regarding breed, gender, and weight was not
included.17 The minimum weight of dogs presented in
this study was 55 lb (25 kg). The median age of dogs in
previous reports was six years13–16 (range, one to 14
years) compared to seven years (range, three to 14 years)
for the cases reported here. Eighty-five percent of dogs
in the previous studies13–16 were male, compared to 60%
of the cases reported here.
Ascites is a common clinical finding on initial exami-
nation of dogs with IPE and was noted at presentation in
all five dogs with IPE in one report.15 In the present
study, ascites was recorded in 17 of 25 records at the
time of initial examination, and it resolved after surgery
in all survivors. In a study of 46 dogs with pericardial
effusion from various causes, patients with concurrent
ascites were statistically less likely to die of their under-
lying disease than dogs without ascities.18 Chronic accu-
November/December 1999, Vol. 35
mulation of pericardial effusion is associated with slowly
developing heart failure. In dogs with IPE, the pericar-
dial sac gradually stretches to accommodate the fluid
until right-sided congestive heart failure and ascites de-
velop. In more aggressive conditions such as neoplasia,
pericardial fluid accumulates more rapidly, resulting in
acute or subacute clinical signs including collapse and
cardiac tamponade, but not ascites.18
Pericardiocentesis followed by medical management
and monitoring for recurrence of clinical signs has been
used successfully to manage cases of pericardial effu-
sion. In a report of 14 dogs with IPE, six dogs survived
for a median of three years (range, 0.5 to 6 years) follow-
ing treatment by pericardial drainage alone; however,
two required additional pericardiocentesis.13 In another
study involving eight dogs with IPE, one dog treated
with pericardiocentesis survived for 54 months, although
interim pericardiocentesis was necessary.14
Disadvantages of conservative management of peri-
cardial effusion include risk of sudden, life-threatening
cardiac tamponade; inability to examine thoracic struc-
tures at the time of surgery to rule out other causes of
pericardial effusion, including tumor or foreign body;
and the potential for development of constrictive peri-
carditis.19 Two dogs previously diagnosed with IPE de-
veloped constrictive pericarditis three months and 1.5
years after treatment by pericardial fenestration and
pericardiocentesis, respectively.19,20
The choice of surgical approach to the pericardium in
this series of cases was at the discretion of the surgeon
and was based on results of presurgical evaluations,
including ultrasound, as well as experience and prefer-
ence of the surgeon. Advantages of median sternotomy
include visualization of the entire pericardial sac, heart,
and thorax. Advantages of a right thoracotomy include
access to the right atrial appendage and decreased oper-
ating time. Disadvantages of median sternotomy include
the need for specialized equipment such as an osteotome
and oscillating saw, as well as increased operating time.
The major disadvantage of right lateral thoracotomy is
the inability to visualize the left side of the heart and
thoracic cavity, including the left side of the pericardial
sac and the left phrenic nerve, requiring some blind
dissection of the pericardium ventral to the phrenic nerve
on that side. Although more postoperative pain and a
higher incidence of wound complications have been as-
sociated with median sternotomy, this was not the au-
thors’ experience. Prophylactic antibiotics and pain
medication were used routinely.
The use of a pericardial fenestration (i.e., pericar-
diotomy) in four cases in this study did not affect mor-
bidity or mortality. Although utilization of single or
multiple small openings in the pericardium for drainage
of fluid into the thoracic cavity will be effective initially,
adhesions or fibrosis may result in reaccumulation of
fluid and recurrence of clinical signs. If a substantial
November/December 1999, Vol. 35 Idiopathic Pericardial Effusion 525

portion of the diseased pericardium is not removed, con-
strictive pericarditis may result.15 All pericardectomies
in this study were performed ventral to the phrenic nerve,
although some surgeons prefer to perform a total
pericardectomy.21
The etiology of IPE was not determined from clinical
or histopathological data in this series of cases and re-
mains unknown. There is no evidence that this condition
has a viral or immune-mediated basis as has been postu-
lated.14 It appears from the histological evaluation of
tissues that pericardial blood vessels and/or lymphatics
are the target of the disease process. The presence of
“onion skin” layers of fibrosis around blood and lym-
phatic vessels in addition to evidence of old and recent
foci of hemorrhage indicate a chronic, progressive patho-
physiology. A histopathological classification of chronic-
active pericarditis has been applied to this condition.15
Many pericardectomy cases in previous studies were
monitored for only a minimal period of time after sur-
gery or were lost to follow-up. Only three of 12 dogs in
previous studies that had pericardectomy were followed
for at least 18 months.13–16 In another study, 13 dogs
with nonneoplastic pericardial disease that underwent
pericardectomy (including 10 dogs with IPE) survived
for a median of 26 months (range, six days to 48
months). 17 In the present study, seven long-term
survivors (Group III) died 18 to 72 months after
pericardectomy, while 11 were still alive at 20 to 96
months. None of these dogs developed significant prob-
lems related to the surgical procedure or recurrence of
clinical signs of IPE.
Idiopathic pericardial effusion is primarily a disease
of middle-aged, large- and giant-breed dogs. The data
presented here supports subtotal pericardectomy as the
diagnostic method and treatment of choice for dogs sus-
pected of having IPE. Differential diagnosis for pericar-
dial effusion includes tumor, foreign body, and infection.
It is only possible to make a tentative diagnosis of IPE
prior to thoracotomy. The resected pericardial sac should
be evaluated by a veterinary pathologist. Prognosis is
good for a complete recovery in dogs with IPE that
undergo pericardectomy and are discharged from the
hospital.
7. Aronsohn MG. Cardiac hemangiosarcoma in the dog: a review of 38 cases.
J Am Vet Med Assoc 1985;187:922–6.
8. Cobb MA, Brownlee SE. Intrapericardial neoplasia in 14 dogs. J Sm Anim
Pract 1992;33:309–16.
9. Aronson LR, Gregory CR. Infectious pericardial effusion in five dogs.
Vet Surg 1995;24:402–7.
10. Bonagura JD. Electrical alternans associated with pericardial effusion in the
dog. J Am Vet Med Assoc 1981;178:574–9.
11. Bonagura JD, Pipers FS. Echocardiographic features of pericardial effusion
in dogs. J Am Vet Med Assoc 1981;179:49–56.
12. Thomas WP, Reed JR, Gomez JA. Diagnostic pneumopericardiography in
dogs with spontaneous pericardial effusion. Vet Rad 1984;25:2–16.
13. Gibbs C, Gaskill CJ, Darke PGG, Wotton PR. Idiopathic pericardial
haemorrhage in dogs: a review of fourteen cases. J Sm Anim Pract
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