Companion animal practice

Diagnostic approach to anaemia in cats

In Practice: first published as 10.1136/inp.e4889 on 30 July 2012. Downloaded from http://inpractice.bmj.com/ on 10 October 2018 by guest. Protected by copyright.
Séverine Tasker

Anaemia is commonly encountered in feline patients because cats are

Séverine Tasker graduated
from the University of Bristol in
1994 and worked for the PDSA
before moving to the University
of Edinburgh to complete a Feline
Advisory Bureau residency in feline
medicine. She then moved back
to the University of Bristol where
she received a PhD investigating
feline haemoplasmas. She is
currently senior lecturer in small
animal medicine at the University
of Bristol where she is involved
with the Feline Centre and the
Molecular Diagnostic Unit of
Langford Veterinary Services, and
has active research interests in
infectious diseases, particularly
haemoplasma infections and feline
infectious peritonitis.
particularly prone to developing anaemia due to the shorter lifespan
(70 days) of the feline red blood cell and the lower blood volume of cats
compared with other species. However, cats have different types of
haemoglobin that are thought to enable them to tolerate anaemia with
relative ease, particularly chronic anaemia. Indeed, they may only exhibit
clinical signs when anaemia becomes very severe. This article focuses on the
diagnostic approach to anaemia in cats, but pertinent points on treatment
are described where appropriate.
Anaemia results in reduced oxygenation of the allows crude in-house evaluation of the plasma; is it
kidneys, which stimulates erythropoietin (EPO) icteric, which could indicate the presence of acute
release, which in turn stimulates the bone marrow severe haemolysis or liver disease, or is it red, consist-
to increase red blood cell (RBC) production. This ent with haemolysis?
new RBC production indicates an appropriate regen-
erative response in the bone marrow, resulting in a Haemoglobin, mean cell volume, red
regenerative anaemia. Regenerative anaemia arises cell distribution width and mean cell
due to blood loss or haemolysis. If the bone marrow haemoglobin concentration
response is inappropriate a non-regenerative anaemia Haemoglobin (Hb) is a reliable parameter in routine
will result. Most anaemias in cats are non-regenera- haematology, which measures the oxygen carrying
tive in type. Cats may only show clinical signs (Box 1) capacity of the blood.
when the anaemia becomes very severe. The mean cell volume (MCV) indicates the
­average size of the RBCs and is only abnormal if
there are enough abnormal RBCs to pull the mean
Laboratory investigation value out of a wide reference range. Normocytic

There are a number of relatively simple initial tests

that can be performed to investigate the severity and
cause of anaemia. Box 2: Definition and severity of
anaemia
Packed cell volume
Anaemia is defined by reduced numbers of red blood
Spinning of a capillary microhaematocrit tube con- cells (RBCs) or decreased haemoglobin content or
taining anticoagulated blood (three minutes at decreased packed cell volume (PCV). Note the different
12,500 g) is a simple, accurate and rapid way of deter- PCV ranges that reflect the severity of anaemia in cats
mining packed cell volume (PCV), to document the compared with dogs in the table below. The reference
doi:10.1136/inp.e4889 range for PCV in the cat is around 25 to 45 per cent.
Provenance: Commissioned
presence and severity of any anaemia (Box 2). It also
Haemoconcentration due to dehydration can mask
and peer-reviewed
the degree of anaemia, so haematological parameters
should be reassessed after rehydration. Intravenous
fluid therapy should be carefully administered in cats
Box 1: Possible clinical signs of feline anaemia with chronic (severe) anaemia (see Box 4).
■■ Pallor
Packed cell volume (%)
■■ Lethargy/weakness
■■ Jaundice (seen with acute severe haemolysis or concurrent liver disease) Severity of anaemia Feline Canine
■■ Fever may indicate an infectious cause such as Mycoplasma haemofelis infection
■■ Pica is occasionally reported Mild 20–24 30–37
■■ Compensatory tachycardia (with or without a haemic murmur) and/or tachypnoea may Moderate 14–19 20–29
be present with more acute or severe anaemia Severe 10–13 13–19
■■ Splenomegaly, and possibly hepatomegaly, may be evident, reflecting extramedullary
haematopoiesis, red blood cell sequestration or haemolytic activity Very severe <10 <13

370 In Practice July/August 2012 | Volume 34 | 370–381


Fig 1: Regenerative blood smear. Polychromasia and
anisocytosis are features of regeneration that are
visible in this modified Wrights-stained blood smear
(×500) from a cat with a regenerative anaemia due to
gastrointestinal blood loss. Polychromasia is visible in
the polychromatophilic cells (black arrows); these cells
are likely to be aggregate reticulocytes (immature red
blood cells) but new methylene blue (NMB) staining
is required to confirm this. Variation in red blood cell
(RBC) size is seen, called anisocytosis, and a nucleated
RBC (red arrow) is also visible. The granular structures
are platelets (blue arrows)
cells have normal MCV, macrocytic cells have
increased MCV and microcytic cells have reduced
MCV. Regenerative anaemias are usually macrocytic
because reticulocytes have higher MCVs than RBCs,
but macrocytosis can also be seen with non-regener-
ative anaemias associated with feline leukaemia virus
(FeLV) infection or myelodysplasia (see later).
The red cell distribution width (RDW) estimates
the degree of anisocytosis (variation in RBC size) pre-
sent. A raised RDW reflects the presence of increased
numbers of macrocytes, microcytes or both.
The mean cell haemoglobin concentration
(MCHC) indicates the average concentration of Hb
per RBC. A reduced MCHC reflects hypochromasia,
and regenerative anaemias are usually hypochromic
(and macrocytic) because reticulocytes have higher
MCVs and lower Hb content than mature RBCs.
Examination of an air-dried, stained
blood smear
Blood smear examination can provide rapid in-house
assessment of anaemia. In-house staining (eg, Diff-
Quik, Leishman’s) can be performed. A number of
basic features are relatively easy to recognise—for
example, the presence of polychromasia, anisocyto-
sis, nucleated RBCs (NRBCs) (Fig 1). NRBCs usu-
ally reflect active regeneration but are also seen with
splenic dysfunction, shock or bone marrow disorders.
However, a specialist haematologist should always be
consulted to obtain the maximum information from
a blood smear.
Reticulocyte count
The reticulocyte count quantifies the bone marrow
response to determine if the anaemia is regenerative
or non-regenerative. Reticulocytes are only identi-
fiable with vital stains such as new methylene blue
(NMB), which clumps material in reticulocytes, thus
allowing them to be visualised. Reticulocytes cor-
respond to the polychromatic cells on a routinely
stained blood smear.
Companion animal practice
Cats have punctate and aggregate reticulocytes.
Aggregate reticulocytes have multiple (more than
six) small dark blue cytoplasmic granules, in lines,
chains or clumps, whereas punctate reticulocytes have
only a few (two to six) cytoplasmic dots (Figs 2 and
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3). Aggregates last in the circulation for about a day
before maturing further into punctates that then sur-
vive in the circulation for up to 10 days. Only aggre-
gates reflect recent bone marrow RBC production so
these are the reticulocytes included in feline reticulo-
cyte counts, especially when evaluating cats with mod-
erate to pronounced anaemia. Reticulocyte counts are
routinely performed in commercial diagnostic labora-
tories, but can be done in-house too (Box 3).
Total serum protein
Measurement of total serum protein (TSP) is usually
performed when submitting blood for a biochemis-
try profile. However, total plasma protein can also
be measured rapidly in-house using a refractometer.
When PCV is determined using a microhaematocrit
tube, a few drops of the derived plasma are placed
on the refractometer prism by carefully breaking
the capillary tube after scoring it to give a reading
for total plasma protein. Measurement of TSP or
total plasma protein can be helpful in differentiat-
ing blood loss anaemia (protein usually low or low-
normal) from haemolysis (protein usually normal
or high).
Classification of anaemia
■■ Regenerative: haemorrhagic/blood loss
■■ Regenerative: haemolytic
■■ Non-regenerative
The above classification is useful in the diagnos-
tic approach to anaemia. However, in cats multiple
mechanisms and diseases often contribute to the
development of anaemia, so simple classification of
the anaemia may not be possible. Also, important
factors that can make regenerative causes of anaemia
appear non-regenerative must always be considered
(Box 4).
Regenerative anaemia: blood loss
Acute blood loss
Acute blood loss is common in cats, particularly
after major trauma. Haemostatic disorders are
less common but are seen with liver disease and
rodenticide toxicity. Systemic amyloidosis, a rare
Fig 2: Feline reticulocytes. Unlike the dog, cats have two
types of reticulocytes: aggregate and punctate. The
aggregates reflect active regeneration and are those
counted in feline reticulocyte counts
In Practice July/August 2012 | Volume 34 | 370–381 371
Companion animal practice
Fig 3: Feline reticulocytes. A new methylene blue-
stained blood smear is shown (×1000). Examples of
aggregate reticulocytes are indicated by black arrows
whereas punctate reticulocytes are shown by red
arrows. The aggregates reflect active regeneration
and are those counted in feline reticulocyte counts
condition seen in young to middle-aged Siamese
and related breeds, can cause spontaneous liver rup-
ture and abdominal haemorrhage. Gastroduodenal
ulceration and bleeding, due to neoplasia (mast
cell tumours, gastrinoma, lymphoma), non-steroi-
dal anti-inflammatory drug (NSAID) toxicity and
inflammatory bowel disease, can also result in
significant acute blood loss. Hypovolaemic shock,
rather than anaemia, is the most worrying initial
consequence of acute severe blood loss. Cats with
ongoing blood loss (such as during major surgery)
that are receiving intravenous fluids are protected
from hypovolaemia, and if bleeding continues such
patients can rapidly become anaemic.
Chronic blood loss
Chronic blood loss is less common in cats, but can
occur with severe flea or lice infestation in kittens, or
with chronic gastrointestinal or urogenital blood loss.
Box 3: Feline reticulocyte counts
Reticulocyte counts quantify the degree of regeneration present, helping to determine
possible causes of the cat’s anaemia by differentiating regenerative (blood loss or
haemolytic causes) from non-regenerative anaemias.
Performing a reticulocyte count in cats
■■ Mix equal parts (volume or drops) of EDTA blood and new methylene blue (NMB)
stain
■■ Leave to stand for five to 20 minutes
■■ Mix again gently and make a blood smear and rapidly air dry
■■ Count percentage of aggregate reticulocytes in 500 to 1000 red blood cells (RBCs).
This is the per cent (%) reticulocytes present
■■ Use this in the equation below to calculate the absolute aggregate reticulocyte
count, which takes into account the degree of anaemia present by incorporating the
RBC count in the equation.
This count can be used
Regenerative response Absolute reticulocyte
to quantify any degree of count (x109/l)
regeneration present Negligible <50
Mild 50–100
Absolute aggregate
reticulocyte count (x109/l) = Moderate 100–200
% aggregate reticulocytes x
Substantial >200
RBC count (x1012 /l) x10
372 In Practice July/August 2012 | Volume 34 | 370–381
Diagnostic features of blood loss
A rising reticulocyte count is often not evident for
three to five days (the pre-regenerative phase) and then
peaks at five to seven days, although PCV may take
up to two to three weeks to return to normal after
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bleeding. Regeneration is also indicated by anisocy-
tosis, polychromasia and sometimes NRBCs on blood
smears. Hypoproteinaemia may occur in the first week
after bleeding, but persistent anaemia and hypopro-
teinaemia suggest continuing blood loss. Chronic
external blood loss may eventually lead to iron defi-
ciency and a non-regenerative or poorly regenerative
anaemia. Kittens have low body iron stores and are
therefore most susceptible to iron deficiency, charac-
terised by microcytic hypochromic anaemia.
Further investigation of blood loss
Blood loss is usually suspected using standard diag-
nostic tests. Haemostasis (platelet count and buccal
mucosal bleeding time for primary haemostasis, pro-
thrombin time and activated partial thromboplastin
time for secondary haemostasis) should be evaluated
together with potential gastrointestinal, urinary and
body cavity haemorrhage via parasitology, urine anal-
ysis, and thoracic and abdominal imaging. If chronic
blood loss with iron deficiency anaemia is suspected,
ideally iron status should be evaluated although inter-
pretation is difficult in cats. Because cats do not nor-
mally have stainable iron stores in the bone marrow,
bone marrow samples cannot be evaluated for iron
status. Faecal occult blood testing, to test for gastroin-
testinal bleeding, is also difficult because cats should
be maintained on a meat-free diet for three to five days
before sampling. Raised urea concentrations relative
to creatinine may support the presence of gastrointes-
tinal bleeding. TSP may be helpful in differentiating
blood loss anaemia (protein usually low or low-nor-
mal) from haemolysis (protein usually normal or high).
Treatment pointers for blood loss
If blood loss is apparent and is acute and severe, local
pressure, topical adhesives, bandages and tourniquets
can be used as appropriate. Vitamin K1 treatment (2.5
mg/kg subcutaneously on the first day then 0.25 to 2.5
mg/kg orally in divided doses) for at least a week, and
up to six weeks (depending on rodenticide type ingest-
ed), is indicated for rodenticide toxicity. Prothrombin
times are measured 24 hours after stopping vitamin
K1 treatment to determine if continued treatment is
required. Vitamin K1 treatment is also indicated for
liver-associated coagulopathies (0.5 mg/kg subcu-
taneously twice a day, two to three times before, for
example, surgery for a liver biopsy, and every seven
to 21 days thereafter) to try and correct coagulation
times. If gastrointestinal blood loss is occurring, for
example, due to gastrointestinal lymphoma, kidney
or liver disease, or NSAIDs, gastroprotectants (eg,
famotidine, ranitidine or omeprazole, and sucralfate)
should be administered.
Regenerative anaemia: haemolysis
Both extravascular (when RBCs are removed by
macrophages in the spleen, liver and bone marrow)
 Companion animal practice

and intravascular (when RBCs are destroyed within ■■ Infections: FeLV, haemoplasmosis (particularly
the vascular system) haemolysis can occur in cats. Mycoplasma haemofelis), babesiosis, cytauxzoonosis.
Extravascular haemolysis is more common. When ■■ Oxidant injury such as exposure to chemicals and
haemolysis is mediated by antibodies attached to the some disease states can result in a Heinz body
surface of RBCs, this is termed an immune-mediated haemolytic anaemia.

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haemolytic anaemia (IMHA). ■■ Hypophosphataemia can cause intravascular hae-
molysis if severe (<0.35 mmol/l), due to depletion
Causes of haemolysis in cats of RBC energy supply. Hypophosphataemia is seen
■■ Primary IMHA: in some cases no underlying with diabetes mellitus, hepatic lipidosis, re-feeding
causes of IMHA can be identified and such cases syndrome and the oral administration of phosphate-
are referred to as primary IMHA. This is a com- binding antacids.
mon form of IMHA in the dog and was thought ■■ Microangiopathic haemolytic anaemia results from
to be rare in the cat, but recent reports (Kohn and RBC damage due to abnormal vascular endothelium
others 2006) suggest otherwise. or fibrin deposition within vessels (schistocytes –
■■ Secondary IMHA: this can arise secondary to fragmented RBCs – may be visible on blood smears).
infectious agents such as FeLV, haemoplasmas ■■ Inherited RBC defects: osmotic fragility syndrome
and feline infectious peritonitis (FIP), drugs (eg, and pyruvate kinase (PK) deficiency are both
methimazole, trimethoprim-sulphonamides), reported in certain breeds, particularly Abyssinians
neoplasia (eg, lymphoma, myeloproliferative dis- and Somalis.
orders), blood transfusion reactions and neonatal
isoerythrolysis. Blood transfusion reactions and Diagnostic features of haemolysis
neonatal isoerythrolysis are mediated by hae- As with blood loss, a rising reticulocyte count occurs
molysis of RBCs as a result of incompatibility of with haemolysis, but is not evident for three to five
blood types between the donor and the recipient, days (the pre-regenerative phase) and then peaks at
or queen and kitten, respectively. Neonatal iso- five to seven days. Regeneration is indicated by aniso-
erythrolysis is one of the few causes of intravascu- cytosis, polychromasia and sometimes NRBCs on
lar haemolysis in cats. examination of stained blood smears. Some IMHAs,

Box 4: Regenerative versus non-regenerative anaemia

Classifying anaemias as regenerative or non-regenerative is helpful. The diagram below shows the major differentials to be considered for each
category, together with factors that can influence categorisation of the anaemia.

Anaemia

Regenerative anaemia Non-regenerative anaemia

Haemolysis Blood loss Pre-regenerative Secondary Primary bone

anaemia suppression of marrow disease
¥  Primary  immune-­‐mediated  haemoly1c   ¥  Trauma  
anaemia   ¥  Gastrointes1nal  bleeding  e.g.  NSAIDs,  
bone marrow
¥  Following  the  onset  of   ¥  Pure  red  cell  aplasia;  an  
¥  Secondary  immune-­‐mediated  haemoly1c   neoplasia,  kidney  disease   haemolysis  or  blood  loss,   from systemic immune-­‐mediated    condi6on  of  
anaemia  e.g.  due  to  lymphoma,  drugs,   ¥  Urogenital  bleeding   it  takes  3-­‐5  days  for   disease the  bone  marrow  or  secondary  
haemoplasmas,  transfusion  reac6ons,  FeLV,   ¥  Coagulopathies  e.g.  liver  disease,   re1culocytes  to  be   to  FeLV  infec6on  
neonatal  isoerythrolysis   roden6cide  toxicity   released  from  the  bone   ¥  Anaemia  of   ¥  Aplas1c  anaemia  e.g.  
¥  Heinz  body  haemoly1c  anaemia  e.g.  onion   ¥  ‘Menrath'  mouth  ulcers  -­‐  rupture  of   marrow  and  appear  in   inflammatory  disease   retroviral  infec6on,  drugs,  
or  paracetamol  toxicity,  diabe6c  ketoacidosis,   pala6ne  blood  vessels     the  circula1on   e.g.  infec6ons,   starva6on  
lymphoma     ¥  Systemic  amyloidosis  can  cause   ¥  During  these  ini6al  3-­‐5   inflamma6on,  neoplasia   ¥  Myelodysplas1c  syndrome  
¥  Hypophosphataemia  e.g.  diabetes  mellitus,   spontaneous  liver  rupture  &  abdominal   days  the  anaemia  will   ¥  Chronic  kidney   secondary  to  FeLV  or  other  
hepa6c  lipidosis,  refeeding  syndrome   haemorrhage  in  Orientals  &  Siamese       appear  to  be  non-­‐ disease   bone  marrow  diseases  
¥  Inherited  erythrocyte  defects  e.g.  pyruvate   regenera1ve;  called  the   ¥  Some  FIV  and  some   ¥  Myeloprolifera1ve  diseases  
kinase  deficiency  in  Abyssinians  &  Somalis   NB.  Chronic  external   pre-­‐regenera1ve  phase   FeLV-­‐associated   e.g.  leukaemias  
¥  Microangiopathic  haemoly1c  anaemia  e.g.   blood  loss  will  lead  to  a   anaemias     ¥  Myelophthisis  is  seen  with  
disseminated  intravascular  coagula6on   poorly  regenera1ve  iron-­‐   myelofibrosis,  leukaemias  etc.  
deficiency  anaemia  e.g.  
severe  fleas  in  kiNen   FeLV    infec1on  &  myelodysplas1c  syndrome  
can    both  cause  a  macrocy1c  anaemia,  
despite  being  non-­‐regenera6ve  
Concurrent  disease  can  impair  the  regenera1ve  response  
e.g.  FeLV  infec6on,  chronic,  infec6ous  and  inflammatory  
diseases  (such  as  cat  flu)  can  all  reduce  the  marrow  
response  to  anaemia  making  regenera6ve  causes  of  
anaemia  appear  non-­‐  or  less  regenera6ve  

FeLV Feline leukaemia virus, FIV feline immunodeficiency virus, NSAIDs non-steroidal anti-inflammatory drugs

In Practice July/August 2012 | Volume 34 | 370–381 375

Companion animal practice
Fig 4: Feline Heinz bodies. A new methylene blue-
stained blood smear is shown (×1000). Arrows indicate
the blue Heinz bodies on the periphery of many red
blood cells. These typically indicate oxidative damage
and do not stain well with conventional Romanowsky-
type stains such as Diff-Quik
however, are non-regenerative in nature due to
immune targeting of bone marrow precursors. Unlike
anaemia due to haemorrhage, serum protein concen-
trations remain normal, or are high, with haemolysis,
unless concurrent disease affects these. Haemoglobin,
released from haemolysed RBCs, is metabolised to
unconjugated bilirubin which is then very efficiently
taken up by hepatocytes, conjugated and excreted into
bile. Only massive acute haemolysis overwhelms this
process, leading to jaundice (icterus) with bilirubinae-
mia with or without bilirubinuria. Jaundice can occur
with both extravascular and intravascular haemolysis,
whereas haemoglobinaemia and haemoglobinuria are
features of intravascular haemolysis only, where mas-
sive release of haemoglobin directly into the circula-
tion overwhelms plasma binding of the haemoglobin.
In dogs, the presence of spherocytes (small, spheri-
cal erythrocytes with lack of central pallor) on exami-
nation of a stained blood smear usually specifically
indicates that the haemolysis is immune-mediated.
However, spherocytes are difficult to recognise in cats
as feline erythrocytes lack central pallor and therefore
no one can consistently identify spherocytosis in the
cat. This makes diagnosis of IMHA much more diffi-
cult in cats. Cats also lack the typical strong leucocyto-
sis and left shift seen usually in dogs with IMHA. The
presence of large numbers of Heinz bodies suggests
exposure to oxidant damage. Heinz bodies are clumps
of precipitated haemoglobin that are colourless with
routine stains (such as Wright-Giemsa or Diff-Quik)
but are blue-green on slides stained with NMB (Fig 4).
Box 5: Slide agglutination test (SAT)
Four to 10 drops of normal (0.9 per cent) saline and one drop of whole EDTA-
anticoagulated blood are mixed on a glass microscope slide and the mixture is
gently swirled by moving the slide and looking at the blood mixture against a white
background. The SAT is positive if distinct red speckles become visible within a few
minutes; this is gross macroscopic agglutination. Examination of the blood under the
microscope, by adding a coverslip, is recommended so that further confirmation of the
presence of agglutination (random disorganised clumping of red blood cells [RBCs]),
compared to rouleaux (organised stacking of RBCs), can be made. Rouleaux formation
occurs naturally in some cats, and is macroscopically identical to true agglutination. The
addition of saline in the slide agglutination test disperses rouleaux but has no effect on
agglutination.
376 In Practice July/August 2012 | Volume 34 | 370–381
In cats Heinz bodies tend to be single and uniform in
size and can become very large.
Further investigation of haemolysis
Potential causes of haemolytic anaemia may be
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apparent from the history (eg, potential ingestion of
onions in baby food or soup, travel to areas where
infectious causes of haemolysis such as Babesia spe-
cies are endemic). Serum biochemistry (including
serum phosphate) is helpful to screen for underlying
systemic diseases and hypophosphataemia. Other
investigations can include FeLV testing, PCR testing
for feline haemoplasmosis, and performing thoracic
and abdominal imaging to assess for neoplasia or
other underlying diseases. Tests to investigate feline
IMHA include the slide agglutination test (SAT) and
the Coombs’ test.
The SAT (Box 5) is a simple test that detects severe
agglutinating IMHA; the RBCs of cats suffering
from this form of IMHA are coated so heavily with
antibodies and complement that they spontaneously
agglutinate, forming clumps visible to the naked eye.
The diagnosis of IMHA with a negative SAT may be
supported by Coombs’ testing (Tasker and others
2010). Coombs’ testing detects the presence, and can
describe the nature of, erythrocyte-bound antibod-
ies, although positive results may occur with hyper-
globulinaemia, pancreatitis and myelodysplastic
syndromes. Bone marrow examination may be useful
in cases of non- or poorly-regenerative IMHA.
Haemoplasma-associated haemolytic
anaemia
Several species of haemoplasma infect cats:
Mycoplasma haemofelis is the most pathogenic spe-
cies, able to cause anaemia in immunocompetant cats,
while ‘Candidatus Mycoplasma haemominutum’ and
‘Candidatus Mycoplasma turicensis’ are less pathogen-
ic and generally only result in anaemia if concurrent
disease is present. Diagnosis is only reliably achieved
by PCR. Treatment comprises doxycycline (10 mg/kg
once a day orally) for three to six weeks; ensure dos-
ing is always followed by a small amount of food or
syringing of water to encourage complete swallowing
of tablets into the stomach, as some doxycycline for-
mulations have also been associated with oesophagitis
and oesophageal strictures in cats. Fluoroquinolones
may also be effective for the treatment of haemoplas-
mosis. Adjunctive prednisolone treatment, to address
any immune-mediated component of haemoplasma-
induced haemolysis, has been recommended by some,
but in the author’s opinion effective antibiotic therapy
alone is adequate treatment for haemoplasmosis, even
in the face of a positive SAT or Coombs’ test (Tasker
2010). Response to treatment can be monitored via
haematology and quantitative PCR tests, the latter
showing a reduction in organism numbers in the blood
during and following effective antibiotic treatment.
The prognosis for haemoplasmosis is good if appropri-
ate therapy is started quickly.
Immune-mediated haemolytic anaemia
As described above, the SAT and Coombs’ test can be
helpful in the diagnosis of feline IMHA, indicating the
presence of erythrocyte-bound antibodies, although

these tests are not completely sensitive or specific for
IMHA. Since IMHA can be secondary to a number of
underlying causes, if an underlying cause is identified,
this must be treated if possible (for example, if IMHA
is believed to be secondary to drug administration,
then stop the drug). However, increasing numbers of
feline IMHA cases appear to be primary cases with-
out any apparent underlying causes; these are treated
with immunosuppressive doses of prednisolone (2 to
4 mg/kg/day orally, starting at low dose) for at least
four weeks, gradually tapering therapy while the cat
is monitored closely via haematology and reticulocyte
counts. Gastroprotectants may be used to try to pre-
vent ulcerative side effects of prednisolone, although
the preventative effects of any anti-ulcerogenic drug
for steroid-induced ulceration in cats remains unprov-
en. Ciclosporin (2.5-5 mg/kg twice a day orally) can
be tried as an immunosuppressive agent if predni-
solone alone is not adequate. If ciclosporin is effec-
tive, the prednisolone dose can start to be tapered
after a few days. Therapeutic levels of cilcosporin in
the blood can be monitored but this is not usually
necessary. However, an awareness of potential prob-
lems associated with immunosuppression (eg, severe
toxoplasmosis, recrudescence of herpes virus disease)
due to ciclosporin (particularly in combination with
prednisolone) is imperative when using this drug.
Chlorambucil (2 mg per cat every 48 hrs [lower doses
may be effective] for two to four weeks then tapered
to lowest effective dose) is another agent that may be
used to treat IMHA in combination with predniso-
lone if the latter is not adequate alone. Recently the
successful use of adjunct treatment with the immuno-
suppressive agent mycophenolate mofetil (Bacek and
Macintire 2011) (unlicensed for use in cats) has been
reported for primary IMHA at a dose of 10 mg/kg
orally twice daily. Bilirubin measurements may also
indicate the degree of ongoing haemolysis. The prog-
nosis for feline IMHA is generally good with appropri-
ate rapid treatment.
Heinz body anaemia
Feline haemoglobin is particularly sensitive to oxida-
tion, so Heinz bodies form readily in feline RBCs.
Methaemoglobinaemia often accompanies Heinz
body formation in cats, as is seen with paracetamol
(acetaminophen) toxicity. Heinz bodies shorten RBC
survival, and the degree of anaemia which results
depends on the rapidity of Heinz body formation,
their size and number, and the severity of damage to
the RBC membrane. Anaemia is more likely to result
from Heinz body formation if the bodies are large
and affect more than 30 per cent of RBCs.
Cats are particularly sensitive to paracetamol
toxicity due to their relative deficiency in activity of
the enzyme glucuronyl transferase; methaemoglobi-
naemia and Heinz body formation can occur with
paracetamol doses as low as 10 mg/kg, and the rapid
formation of Heinz bodies can lead to significant
anaemia. Other signs include depression, vocalisa-
tion, salivation, facial oedema, vomiting, hyperven-
tilation, icterus and cyanosis. Laboratory evidence
of hepatotoxicity generally develops 24 to 36 hours
after ingestion. Onions, propylene glycol (a food
additive and preservative), some fish-based diets,
Companion animal practice
diabetic ketoacidosis, hyperthyroidism and neoplasia
(especially lymphoma) have also been associated with
Heinz body formation.
Treatment of Heinz body anaemia should
include removal of the inciting cause, if possible.
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Paracetamol toxicity is addressed via acetylcysteine
(now available through the ToxBox service at http://
www.vpisuk.co.uk/portal/Vets/Toxbox/tabid/145/
Default.aspx), cimetidine and vitamin C treatment,
although limiting absorption and inducing vomit-
ing is indicated if treatment can be started within
two to four hours of ingestion. Blood transfusions,
oxygen and fluid support may be required. SAMe
(S-adenosylmethionine) treatment may also be ben-
eficial. Prognosis is guarded for paracetamol toxicity
unless rapid treatment is started.
Pyruvate kinase deficiency
Pyruvate kinase (PK) is an enzyme critical to RBC
energy metabolism, and PK deficiency leads to RBC
haemolysis. PK deficiency is an autosomal recessive
inherited trait in Abyssinians and Somalis. PK defi-
ciency has also recently been found in the Bengal and
Singapura breeds. Genetic molecular screening tests
are now available to identify affected and carrier
cats, and disease is known to be prevalent in the UK
(Harvey and others 2007). Over half of those affect-
ed show anaemia associated with PK-induced hae-
molysis, and around 25 per cent will die due to the
disease, with most showing anaemia and/or spleno-
megaly by three years of age. Chronic haemolysis can
lead to the formation of bilirubin choleliths, which
can cause biliary tract obstruction. Management
options include avoiding stress which may precipitate
haemolytic crises, splenectomy and glucocorticoids
(to reduce haemolysis via the macrophage phagocytic
system), and blood transfusions.
Non-regenerative anaemia
Non-regenerative anaemias usually develop gradually
as the diseased bone marrow fails to replace ageing
erythrocytes. Compensatory mechanisms are well
established, enabling cats to cope despite severe anae-
mia in many cases. Primary marrow disorders often
cause moderate to severe anaemia while systemic
disorders tend to produce mild subclinical anaemia,
although exceptions occur.
Causes of non-regenerative anaemia
The major causes of non-regenerative anaemias due to
primary bone marrow disorders or systemic suppres-
sion of the bone marrow are shown in Box 4.
Diagnostic features of non-regenerative
anaemia
Non-regenerative anaemias have minimal anisocytosis
and polychromasia, and a low reticulocyte count; RBCs
are usually normal in size and staining (ie, normocytic
and normochromic). FeLV infection and myelodyspla-
sia, however, may cause a macrocytic non-regenerative
anaemia, while iron deficiency will result in microcytic,
hypochromic anaemia. Bone marrow disorders may
cause concurrent leucopenia and thrombocytopenia.
In Practice July/August 2012 | Volume 34 | 370–381 377
Companion animal practice

Box 6: General treatment pointers for anaemic cats

■■ If the anaemia is severe (packed cell volume (PCV) <13 per cent) and/or has developed acutely, and significant
related clinical signs (see Box 1) are present, a blood transfusion may be required. Blood transfusions must only
be performed after blood typing both the donor and recipient and confirming they are compatible (Barfield

In Practice: first published as 10.1136/inp.e4889 on 30 July 2012. Downloaded from http://inpractice.bmj.com/ on 10 October 2018 by guest. Protected by copyright.
and Adamantos 2011).
■■ Treatment with oxygen-carrying haemoglobin can be lifesaving if blood donors or blood products are not
readily available, and especially if circulatory support is also required if hypovolaemia is present. Oxyglobin
(unlicensed for use in cats) can be used (5 to 10 ml/kg intravenously at a rate of 0.5 to 2 ml/kg/hour).
Oxyglobin (bovine haemoglobin glutamer-200) is a potent colloid so careful monitoring and very slow
administration is imperative when treating cats prone to circulatory overload as pulmonary oedema can result.
This can happen in, for example, cats with cardiac disease (including occult hypertrophic cardiomyopathy),
renal disease, respiratory disease, or indeed any cat with (chronic) severe anaemia as it has recently been
shown that cats with PCVs ≤18 per cent have evidence of volume overload on echocardiography (Wilson
and others 2010). This is thought to arise because of increased intravascular volume occurring as a result
of the haemodynamic compensatory responses that occur with (chronic) severe anaemia, making them
susceptible to congestive heart failure if intravenous fluid or colloidal (eg, Oxyglobin) therapy is given too
rapidly. Following Oxyglobin administration, the PCV typically decreases due to its haemodilution effects,
so haemoglobin should be measured to estimate oxygen carrying capacity. Oxyglobin also interferes with
some colorimetric biochemistry and urine analyses, so ideally urine analysis and serum biochemistry should
be performed before administration. However, Oxyglobin has recently become unavailable and its future
availability is unknown at the time of writing.

Further investigation of non-
regenerative anaemia
Systemic illnesses causing secondary depression
of erythrocyte production can usually be identi-
fied by history, physical examination, haematology
and serum biochemistry. FeLV and feline immuno-
deficiency virus (FIV) testing should be performed.
Measurement of serum EPO concentrations may help
confirm the aetiology of anaemia in a cat with chronic
kidney disease, but is rarely performed. Bone marrow
aspiration cytology and/or core biopsy histopathol-
ogy is essential for establishing a definitive diagnosis
in cats with non-regenerative anaemia due to prima-
ry marrow disorders. Bone marrow samples should
always be interpreted with a concurrent haemogram,
requiring blood sampling at the time of bone marrow
sampling. Bone marrow aspirate samples can also be
submitted for FeLV testing.
Anaemia of inflammatory disease
Anaemia of inflammatory disease (AID) is a very com-
mon cause of anaemia in the cat. AID is also known
as anaemia of ‘chronic’ disease, but ‘inflammatory’
is the preferred term since the anaemia can develop
within one to two weeks or even sooner (within three
to four days) (Ottenjann and others 2006). It is asso-
ciated with a variety of diseases including chronic
infections, inflammation and neoplasia. The anaemia
is mild to moderate (PCV >17 per cent) and usually
normocytic and normochromic. Microcytosis and
hypochromia are occasionally seen. Very rarely AID
causes a severe anaemia that can necessitate blood
transfusion. Clinical signs caused by the anaemia
are usually rare due to its mild nature. Diagnosis and
management of the underlying disease is required;
since AID is often mild, no specific treatment of the
anaemia is usually required.
Chronic kidney disease
Up to 40 per cent of cats with chronic azotaemia and
end stage kidney disease are anaemic. The degree
of anaemia is roughly proportional to the degree of
azotaemia. The anaemia is non-regenerative, normo-
cytic and normochromic. The anaemia arises due to
a combination of factors including decreased renal
EPO production and blood loss due to gastrointesti-
nal ulceration. Some cats with late stage chronic kid-
ney disease (CKD) develop pancytopenia associated
with an aplastic bone marrow. Anaemia is not often a
major cause of clinical signs in CKD patients, but gas-
troprotectants and/or EPO can be considered if gas-
trointestinal ulceration or severe anaemia is present.
EPO treatment is problematic due to its expense and
the likely formation of anti-EPO antibodies follow-
ing treatment, which worsen the severity of anaemia
further. However, reports have appeared recently of
the successful use of a longer acting EPO agent called
darbepoetin, which is less associated with the forma-
tion of anti-EPO antibodies (Chalhoub and others
2012).
Pure red cell aplasia
In pure red cell aplasia (PRCA), anaemia arises due
to selective erythroid bone marrow depletion. PRCA
can be secondary to FeLV infection, when the condi-
tion is invariably fatal, or can be immune-mediated,
sometimes accompanied by a positive Coombs’ test.
Immune-mediated PRCA can be treated by immu-
nosuppressive doses of prednisolone (2 to 4 mg/kg/
day orally, starting at low dose), although response
to treatment can take a few weeks. Gastroprotectants
may be used to try to prevent ulcerative side effects
of prednisolone, although the preventative effects of
any anti-ulcerogenic drug for steroid-induced ulcera-
tion in cats remains unproven. As described under
IMHA above, ciclosporin (Viviano and others 2011)
and chlorambucil are alternative agents that may be
used to treat PRCA.
Aplastic anaemia
In cases of aplastic anaemia, bicytopenia or pan-
cytopenia (where all cell lines in the bone marrow
are affected: RBCs, granulocytes and platelets) is
present, and more than 95 per cent of the marrow
haematopoietic space is occupied by adipose tissue.
FeLV, FIV, parvovirus, toxoplasmosis, ehrlichiosis,

378 In Practice July/August 2012 | Volume 34 | 370–381


feline infectious peritonitis (FIP), late stage CKD
and starvation are potential causes. Agents such
as griseofulvin (particularly in FIV positive cats),
methimazole, chloramphenicol, oestrogen and some
chemotherapy agents can also induce aplastic anae-
mia; if drug-induced, treatment comprises withdraw-
al of the inciting drug. Some cases are idiopathic.
Cats without a treatable underlying cause of aplastic
anaemia carry a grave prognosis.
Myelodysplastic syndrome
Myelodysplastic syndrome (MDS) is associated with
maturation defects in one or more of the haematopoi-
etic cell lines, typically with hypercellular marrow
but concurrent cytopenia in the peripheral blood.
Macrocytosis may be present. MDS can be associated
with FeLV infection or other underlying bone mar-
row diseases. A significant number of cats with MDS
go on to develop leukaemia. Occasionally, MDS with
no underlying aetiology will respond to differentiat-
ing agents (such as cytosine arabinoside), anabolic
steroids or haematopoietic growth factors, but in the
author’s experience a positive response to treatment
is rare.
Myeloproliferative disorders
Myeloproliferative disorders arise due to the abnor-
mal production of any of the marrow precursors,
typically due to neoplasia – for example, infiltration
of the marrow by lymphoid cells secondary to lym-
phoma or leukaemia. Myeloproliferative diseases are
categorised as acute or chronic based on the maturi-
ty of the cells involved. Acute leukaemias have more
than 30 per cent blast cells in the bone marrow and
cells show maturation arrest (eg, acute lymphoblas-
tic leukaemia), whereas chronic leukaemias have less
than 30 per cent blast cells in the bone marrow and
have well differentiated cells with no maturation
arrest (eg, chronic lymphocytic leukaemia, chronic
myeloid leukaemia). Treatment depends on the type
of myeloproliferative disease present, and consists
of supportive therapy (eg, antibiotics for neutrope-
nia, blood transfusion if severe anaemia) as well as
more specific therapy (eg, chemotherapy) if available.
The prognosis is poorer for acute myeloproliferative
diseases compared with chronic myeloproliferative
diseases.
Myelophthisis
Myelophthisis represents a space-occupying lesion
in the bone marrow that inhibits or displaces nor-
mal haematopoietic cells (eg, neoplastic prolifera-
tion in a leukaemia or fibrous tissue in myelofibrosis).
Companion animal practice
Myelofibrosis may be idiopathic or due to chronic
bone marrow disease (eg, myeloproliferative disease).
Conclusion
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Although feline anaemia can arise due to a number
of complex causes, a logical and thorough approach
to the diagnostic investigation of cases can lead the
clinician to establish a definitive diagnosis and insti-
gate appropriate treatment (Box 6). Many tests can
be done in-house, although the value of submitting
blood samples and smears to a diagnostic laboratory
with expertise in feline haematology profiles can-
not be over-emphasised. Primary IMHAs in cats are
more common than previously thought.
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