Red blood cell (RBC) morphologic features

Term Meaning Interpretation

Anisocytosis Variation in size This can be due to increased numbers of large RBC or small RBC, or a
(diameter) combination of both. Some degree of anisocytosis is normal in
animals.This is the smear equivalent of the red blood cell distribution
width (RDW), which is a measure of the variation in RBC volume.
Result reporting: Subjectively graded as mild, moderate or marked.

Acanthocytes Irregularly spiculated Mechanism: Mostly unknown, but speculated to be due to alterations
RBC or “spur” cell in lipid composition of RBC membrane and fragmentation.
Physiologic: Young ruminants (calves).
Disorders: Hemangiosarcoma (canine), liver disease (canine, feline),
disseminated intravascular coagulation (DIC) (canine), vasculitis
(canine), iron deficiency anemia (canine), possible congenital/inherited
disorder (canine), various other diseases (e.g. renal, gastrointestinal,
cardiac). Largest numbers observed in dogs with hemangiosarcoma.
Result reporting: Subjectively graded as few, moderate, many.
Differentiate from: Echinocytes (regularly spiculated). Can be difficult
in individual animals.
Acuminocyte Fusiform RBC, spindled Mechanism: Likely polymerization of hemoglobin variants.
RBC Physiologic: Young goats, some species of adult goats (Angora), low
numbers in non-anemic camelids.
Diseases: Iron deficiency anemia in camelids, increased numbers seen
in regenerative anemia in goats.
Result reporting: Subjectively graded as few, moderate, many.

Aggregate reticulocyte Aggregates of RNA in a Term used to identify immature RBC with large amounts of RNA that
reticulocyte stain, e.g. precipitate as large chunks or “aggregates” when the blood is
new methylene blue incubated with an intravital dye, such as new methylene blue.
Aggregate reticulocytes correspond to polychromatophilic RBC in a
Romanowsky-stained blood smear (e.g. Wright’s, May-Grunwald-
Giemsa, rapid stains).
Relevance: Indicate a regenerative response in all species. Have a short
half-life in cats (around 12 hours) so indicate the current response by
the bone marrow to an anemia. May not be released from the bone
marrow in mild anemias in cats. Included in a reticulocyte count in dogs
and cats.
Agglutination Clumping of RBC Mechanism: Mediated by antibody bridging of adjacent RBC.
Artifact: EDTA-dependent antibody binding.
Drugs: Heparin therapy (horses).
Disorders: Immune-mediated hemolytic anemia (dog, cat, horse).
Result reporting: Present or absent (not graded).
Differentiate from: Rouleaux formation (does not usually disperse on
saline dilution).
Basophilic stippled RBC RBC with chunky blue Mechanism: Aggregates of RNA due to RBC immaturity or inhibition of
dots in a Romanowsky RNA degradation. Does not require intravital dye precipitation to
stain observe in a regularly stained blood smear (Romanowsky stain).
Physiologic: Regenerative anemia (ruminants in particular, also dogs
and cats but infrequent in the latter).
Pathologic: Lead poisoning (inhibits RNA degradation).
Result reporting: Subjectively graded as few, moderate, many.
Differentiate from: siderocytes (more focal, smaller, lighter blue dots).
Dacryocytes Tear-drop RBC Mechanism: Unknown.
Physiologic?: Low numbers in non-anemic camelids.
Disorders: Iron deficiency (camelids), myelofibrosis (dogs, not a
consistent finding).
Result reporting: Subjectively graded as few, moderate, many.

Drepanocytes Sickled RBC Mechanism: Specific types of hemoglobin form linear polymers under
 oxygenated states (frequently after blood sample collection).
Physiologic: Deer, antelope, sheep (certain breeds) mongoose, genet.
Result reporting: Subjectively graded as few, moderate, many.

Eccentrocytes Hemighost with Mechanism: Oxidant-induced cross-linking of RBC membrane.

“eccentric” central Drugs: Vitamin K1, phenothiazine drenches (horse), new methylene
pallor blue, propofol, acetaminophen (cats).
Disorders: Copper poisoning (sheep), red maple leaf toxicity (horses),
onions (dogs, cats, cattle, horses), Brassica species, e.g. kale
(ruminants), zinc toxicity (dog), naphthalene in mothballs (dog), skunk
musk (dogs, panda), inherited defects (glucose-6-phosphate
dehydrogenase deficiency, flavin adenine dinucleotide deficiency; both
in horses), various diseases in dogs associated with oxidant injury
(lymphoma, diabetes mellitus, anticoagulant rodenticide toxicosis).
Result reporting: Subjectively graded as few, moderate, many.
Echinocytes Regularly Mechanism: Expansion of the outer leaflet of RBC membrane, ATP
spiculated,”burr” cells depletion.
or crenated cells Artifact: Stored (aged) blood, excess EDTA, increased pH.
Drugs: Furosemide (horses), salicylates, phenylbutazone, doxorubicin
(small animals).
Disorders: Electrolyte depletion, glomerulonephritis, pyruvate kinase
deficiency, snake envenomation (rattlesnake, coral snake, viper),
burns, bee stings.
Result reporting: Subjectively graded as few, moderate, many.
Differentiate from: Acanthocytes (irregularly spiculated). This can be
difficult.
Elliptocytes Oval or elongate RBC Three types: Type I (slightly oval), type II (oval), type III (elongate).
Mechanism: In inherited conditions, due to alterations in membrane (band
4.1) or cytoskeletal proteins (spectrin). Unknown mechanism in
myelofibrosis.
Physiologic: Camelids (low numbers).
Drugs: Chemotherapeutic agents.
Disorders: Myelofibrosis (dogs), hereditary disorders in spectrin and band
4.1 (dog).
Result reporting: Subjectively graded as few, moderate, many.
Ghost RBC Lysed RBC Mechanism: Rupture of RBC membrane, releasing hemoglobin and
leaving membrane scaffolds.
Artifact:In vitro hemolysis (poor sample collection, freezing of blood,
aged RBC).
Drugs: DMSO (horse).
Diseases: Intravascular hemolytic anemia, due to immune-mediated
hemolytic anemia in dogs, Babesia infection, copper poisoning in sheep,
zinc toxicity in dogs, Clostridial toxins, hypophosphatemia, acute liver
failure in horses, acute transfusion reaction, neonatal isoerythrolysis in
horses, ruminants (not an exhaustive list).
Result reporting: Present or absent (not graded)
Heinz bodies Refractile or red Indicates oxidant injury. More readily visualized in a reticulocyte (new
inclusions in RBC methylene blue) stain.
Mechanism: Precipitated oxidized hemoglobin.
Diseases: Oxidant injury (see eccentrocytes for diseases). The
hemoglobin of cats is more susceptible to oxidant injury than other
species, so low numbers of Heinz bodies are seen in the blood of non-
anemic cats. In fact, some non-anemic cats can have many small
refractile Heinz bodies due to endogenous (e.g. diabetes mellitus,
hyperthyroidism, lymphoma) or exogenous oxidants (e.g. propylene
glycol). These small Heinz bodies are called “endogenous” Heinz
bodies. In other species, Heinz bodies are associated with an oxidant-
induced hemolytic anemia.
Result reporting: Subjectively graded as few, moderate, many(easier
to do in a new methylene blue stain).
Howell-Jolly body Nuclear remnant or Mechanism: Increased RBC production (regenerative anemia),
 micronuclei decreased removal (by splenic macrophages).
Physiologic: Regenerative anemia, low numbers of Howell-Jolly bodies
can be seen in healthy animals (horses and cats, particularly).
Drugs: Corticosteroids (inhibit splenic removal).
Diseases: Dyserythropoietic syndromes (congenital, neoplasia).
Result reporting: Subjectively graded as few, moderate, many.

Hypochromic RBC Less hemoglobin or Mechanism: Decreased or inhibited hemoglobin production.

hypochromasia Physiologic: Very young animals (physiologic iron deficiency anemia,
easiest to identify in dogs).
Mineral/nutrient deficiency: Iron deficiency (blood loss, nutritional
deficiency), vitamin B6 deficiency (rare), copper deficiency (leads to
iron deficiency), zinc excess.
Diseases: Chronic external blood loss, chronic lead poisoning.
Result reporting: Subjectively graded as mild, moderate, marked.
Differentiate from: Torocytes (normal rim of hemoglobin).
Keratocytes “Bite”, “helmet” or Mechanism: Oxidant or fragmentation injury. Low numbers may be
“blister” cells seen in non-anemic cats.
Diseases: See above disorders for acanthocytes (fragmentation) and
eccentrocytes (oxidant).
Result reporting: Subjectively graded as few, moderate, many.

Macrocytes Bigger RBC Not synonymous with macrocytosis (high MCV). Low numbers of
macrocytes may be seen without a high MCV (insufficient numbers to
increase the MCV above the upper reference limit).
Mechanism: Immature RBC (larger than normal), uptake of water,
altered DNA metabolism.
Breed-associated: Poodles (toy and miniature), possibly Greyhounds.
Artifact: Stored (aged) blood (may be associated with a low mean cell
hemoglobin concentration), hyperosmolality (hypernatremia,
hyperglycemia with the ADVIA hematology analyzer).
Drugs: Interfere with DNA metabolism, e.g. hydroxyurea,
sulfonamides.
Physiologic: Response to regenerative anemia (punctate
reticulocytes).
Mineral/nutrient deficiency: Vitamin B12 deficiency, folate deficiency,
cobalt deficiency, molybdenum excess.
Diseases: Feline leukemia virus infection (cats), congenital
dyserythropoietic syndromes (poll Hereford), myelodysplastic
syndrome, diabetes mellitus (RBC swelling), hyperthyroidism
(unknown mechanism).
Result reporting: Subjectively graded as few, moderate, many.
Microcytes Smaller RBC Difficult to identify true microcytes and RBC are not usually reported as
microcytes in animals with MCV below the lower reference limit for
that species. This term is rarely or not used at Cornell University, since
it is of uncertain relevance and could encompass more diagnostic
shapes, such as spherocytes, schistocytes. Identification of the latter
specific shapes is more informative.
Poikilocytes Variable RBC shapes Mechanism: Various (see specific changes).
(too variable to Physiologic: Young calves and goats, normal in adult Angora goats.
quantify individual Drugs: Chemotherapeutic agents, e.g. doxorubicin.
shapes) Diseases: Liver disease (cats).
Result reporting: Subjectively graded as few, moderate, many.

Polychromatophils Purple RBC or Mechanism: Immature RBC which contain abundant RNA (ribosomes,
polychromasia polyribosomes). Correspond to aggregate reticulocytes.
 Physiologic: Can be seen in normal dogs and cats in low numbers. Part
of a regenerative response.
Result reporting: Subjectively graded as mild, moderate, marked.

Punctate reticulocyte Small dots of RNA in a Term used to identify immature RBC with small amounts of RNA that
reticulocyte stain, e.g. precipitate as small “punctate” dots chunks when the blood is
new methylene blue incubated with an intravital dye, such as new methylene blue. They are
considered more mature than aggregate reticulocytes, because they
contain less RNA. Punctate reticulocytes may be larger than normal
and would correspond to macrocytes in a Romanowsky-stained blood
smear (e.g. Wright’s, May-Grunwald-Giemsa, rapid stains). However,
not all macrocytes are punctate reticulocytes (macrocytes can form
through other mechanisms).
Relevance: Included in a reticulocyte count in dogs, but not cats (can
be counted separately from aggregate reticulocytes by certain
laboratories; this is not done at Cornell University). Have a longer half-
life in cats than aggregate reticulocytes (around 3 days) so do not
indicate the current response by the bone marrow to an anemia. Only
punctate reticulocytes may be released in mild anemias in cats.
Pyknocyte RBC remnant Mechanism: Oxidant injury (remnant after removal of tags of
membrane associated with rupture of eccentrocytes).
Diseases: See above for eccentrocytes.
Result reporting: Not always quantified or reported in hemograms.
Differentiate from: Spherocytes (can only be done by electron
microscopy, however usually accomplished by the company they keep,
i.e. the presence of eccentrocytes would support the cells being
pyknocytes versus spherocytes).
Rouleaux formation Stacking of RBC Mechanism: Decreased negative charge on RBC, usually due to
increased globulins (fibrinogen, immunoglobulins).
Physiologic: Horses, cats, pigs (can be normal in this species).
Diseases: Inflammation (high fibrinogen, polyclonal gammopathy,
restricted oligoclonal gammopathy), antigenic stimulation (polyclonal
or restricted oligoclonal gammopathy), neoplasia of B cells (lymphoma,
chronic lymphocytic leukemia) or plasma cells (multiple myeloma,
extramedullary plasmacytome, solitary myeloma of bone) producing a
monoclonal immunoglobulin. Should be associated with a high total
protein by refractometer or high globulin on a chemistry panel.
Result reporting: Subjectively graded as mild, moderate, marked.
Differentiate from: Agglutination (three-dimensional clumps):
Disperses with saline dilution (1:4 to 1:10 blood:saline)
Schistocytes RBC fragments Mechanism: Shearing of RBC in the circulation due to abnormalities in
or”schizocyte” the vasculature (endothelial cell, fibrin strands, blood flow) or
mechanical RBC fragility (iron deficiency).
Diseases: See above for acanthocytes. Also portosystemic shunts
(altered blood flow).
Result reporting: Subjectively graded as few, moderate, many.

Siderocytes Aggregates of iron, Mechanisms: Aggregates of iron (in lysosomes or mitochondria), due
focal blue/gray to increased iron turnover or inhibition of iron use.
inclusions, siderotic Drugs: Hydroxyzine, chloramphenical.
granules, Diseases: Hemolytic anemia (increased RBC turnover), myelodysplastic
pappenheimer bodies syndrome and acute myeloid leukemia (cats), lead poisoning,
portosystemic shunts, vitamin B6 and copper deficiency in pigs.
Result reporting: Subjectively graded as few, moderate, many.
Differentiate from: Basophilic stippling (coarse chunks of RNA,
diffusely distributed around RBC): Would stain positive for iron with a
Prussian blue stain.
Spherocytes Sphered RBC Mechanism: Removal of membrane by macrophages (trogocytosis).
Artifact: Stored red blood cells (transfusions), feathered edge.
Disease: Immune-mediated hemolytic anemia (primary or secondary to
 infectious agents, drugs), pyruvate kinase deficiency
(spheroechinocytes), fragmentation (low numbers), hemophagocytic
syndrome, histiocytic sarcoma, snake envenomation, inherited band 3
deficiency in Japanese black cattle.
Result reporting: Subjectively graded as few, moderate, many.
Differentiate from: Pyknocytes (context-dependent, the company they
keep, electron microscopy) or microcytes (can be difficult if only a few
but latter are more variable in size).
Stomatocytes RBC with a slit or Mechanism: Expansion of the inner leaflet of the RBC membrane.
mouth-like central Artifact: Blood smear preparation.
pallor (“stoma”) Physiologic: Woodchuck, manatee, dolphin.
Disorders: Hereditary stomatocytosis in dogs (Alaskan Malamute,
Drentje patrishond, standard and miniature Schnauzer, Peek-a-poo,
Pomeranian).
Result reporting: Subjectively graded as few, moderate, many.
Target cell RBC with a bullseye. Only recognized in dogs, which have central pallor.
Codocyte Mechanism: Expansion of the inner leaflet of the RBC membrane, cells
that spread in a smear than normal (leptocytes).
Diseases: Iron deficiency anemia (hypochromic RBC), liver disease, lipid
abnormalities.
Result reporting: Subjectively graded as few, moderate, many.

Torocyte Punched out cell Artifact: Blood smear preparation.

Result reporting: Not usually reported on a hemogram.
Differentiate from: Hypochromasia (normal rim of hemoglobin,
“punched out” central pallor with sharp edges).