Term Meaning Interpretation

Anisocytosis Variation in size This can be due to increased numbers of large RBC or
(diameter) small RBC, or a 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 Mechanism: Mostly unknown, but speculated to be due to

spiculated RBC or alterations in lipid composition of RBC membrane and
“spur” cell 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, Mechanism: Likely polymerization of hemoglobin variants.

spindled 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 Term used to identify immature RBC with large amounts of
in a reticulocyte RNA that precipitate as large chunks or “aggregates” when
stain, e.g. new the blood is incubated with an intravital dye, such as new
methylene blue 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 Mechanism: Aggregates of RNA due to RBC immaturity or
blue dots in a inhibition of RNA degradation. Does not require intravital
Romanowsky stain dye precipitation to 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

“eccentric” central membrane.
 pallor Drugs: Vitamin K1, phenothiazine drenches (horse), new
methylene blue, propofol, acetaminophen (cats).
Disorders: Copper poisoning (sheep), red maple leaf
toxicity (horses, camelids),Pistacia 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

spiculated,”burr” membrane, ATP depletion.
cells or crenated Artifact: Stored (aged) blood, excess EDTA, increased pH.
cells Drugs: Furosemide (horses), salicylates, phenylbutazone,
doxorubicin (small animals).
Disorders: Electrolyte depletion, glomerulonephritis,
pyruvate kinase deficiency, snake envenomation
(rattlesnake, coral snake, viper), burns, bee
stings, Clostridiainfections.
Result reporting: Subjectively graded as few, moderate,
many.
Differentiate from: Acanthocytes (irregularly spiculated).
This can be difficult.

Elliptocytes Oval or elongate Three types: Type I (slightly oval), type II (oval), type III
RBC (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 Refractile or red Indicates oxidant injury. More readily visualized in a

inclusions in RBC reticulocyte (new methylene blue) stain.
Mechanism: Precipitated oxidized hemoglobin.
Diseases: Oxidant injury (see eccentrocytes for diseases).
The hemoglobin of cats is more susceptible to oxidant injury
bodies
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

micronuclei anemia), 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

“blister” cells may be 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 Mechanism: Various (see specific changes).

shapes (too Physiologic: Young calves and goats, normal in adult
variable to quantify Angora goats.
individual shapes) Drugs: Chemotherapeutic agents, e.g. doxorubicin.
Diseases: Liver disease (cats).
Result reporting: Subjectively graded as few, moderate,
many.

Polychromatophils Purple RBC or Mechanism: Immature RBC which contain abundant RNA
polychromasia (ribosomes, 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 Term used to identify immature RBC with small amounts of
in a reticulocyte RNA that precipitate as small “punctate” dots chunks when
stain, e.g. new the blood is incubated with an intravital dye, such as new
methylene blue 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

or”schizocyte” abnormalities in 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

focal blue/gray mitochondria), due to increased iron turnover or inhibition of
inclusions, siderotic iron use.
granules, Drugs: Hydroxyzine, chloramphenical.
pappenheimer Diseases: Hemolytic anemia (increased RBC turnover),
bodies myelodysplastic 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
mouth-like central membrane.
pallor (“stoma”) Artifact: Blood smear preparation.
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 Only recognized in dogs, which have central pallor.
bullseye. 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).

Bovine

Poikilocytosis in a calf

Normal bovine erythrocytes

Bovine erythrocytes are similar in size to horse erythrocytes and have a small amount of central
pallor (with some lacking central pallor). Some degree of anisocytosis can be seen in smears
from healthy cattle. Cattle rarely display rouleaux formation in health or disease. The
approximate erythrocyte lifespan is 160 days.

Polychromatophils are not usually observed in blood smears from healthy non-anemic cattle,
although reticulocytes are released along with macrocytes in response to an anemia. However,
their capacity for regeneration is not as marked as the dog. Basophilic stippling of nucleated and
non-nucleated erythrocytes can be a common finding in ruminants with a regenerative response.

Note that marked poikilocytosis (variation in red cell shape), thrombocytosis (often > 1 million
cells/uL) and microcytosis are features of healthy calf blood (usually under 3 months of age).
Calves can remain microcytic for up to 1 year of age, which is attributed to a physiologic iron
deficiency
Echinocytes

Elliptocytes

Keratocytes

Poikilocytes

Schistocytes
Spherocytes

Hypochromasia