Vet Clin Small Anim

33 (2003) 1207–1222

The complete blood cell count: a powerful

diagnostic tool
Anne M. Barger, DVM, MS
Department of Pathology, University of Illinois, College of Veterinary Medicine,
1008 Hazelwood Drive, Urbana, IL 61801, USA

The complete blood cell count (CBC) is an important and powerful

diagnostic tool as well as a component of a minimum database. It can be
used to monitor response to therapy, to gage the severity of an illness, or as
a starting point for formulating a list of differential diagnoses. Interpreta-
tion of the CBC can be broken down into three sections: evaluation of the
erythrocytes, leukocytes, and platelets. Each of these parameters can be
interpreted individually; however, integration of the data is important for
the highest diagnostic yield.

Erythrocytes
To evaluate erythrocytes appropriately, results of the red blood cell count
(RBC), packed cell volume (PCV), hemoglobin, mean cell volume (MCV),
mean corpuscular hemoglobin concentration (MCHC), and mean corpus-
cular hemoglobin (MCH) must be scrutinized. The peripheral blood smear
can provide additional information through examination of the red blood
cell morphology. The PCV is measured as a percentage of packed cells in
whole blood spun in a microhematocrit tube. The hematocrit, however, is
a calculation using MCV and RBC values from an automated hematology
analyzer. For the purpose of this article, PCV is used throughout.
The evaluation of erythrocytes should begin by interpreting the results of
the PCV and total protein. The PCV is a reflection of the circulating red cell
mass. If the PCV is decreased, the animal is anemic, whereas an elevated PCV
indicates polycythemia. Concurrent measurement of the total protein can
further assist in interpretation of the PCV. When the total protein is elevated,
dehydration or inflammation should be considered. It is important to

E-mail address: abarger@uiuc.edu

0195-5616/03/$ - see front matter Ó 2003 Elsevier Inc. All rights reserved.
doi:10.1016/S0195-5616(03)00100-1
1208 A.M. Barger / Vet Clin Small Anim 33 (2003) 1207–1222

remember that the presence of dehydration may ‘‘mask’’ an anemia. Thus,

the PCV may be normal or even elevated, but once the patient has been
rehydrated, an anemia may be evident. Dehydration may be the underling
cause for polycythemia; fluid losses from the vascular compartment may
result in a relative increase in the red cell mass. A decreased total protein in
an anemic patient could indicate blood loss as the cause of anemia.

Anemia
Anemia is characterized by a decreased PCV, hemoglobin, and RBC in
a normally hydrated animal. Further evaluation of the CBC is important to
classify the anemia as regenerative or nonregenerative. This is likely to assist
in determining the underlying cause of the anemia. The reticulocyte count is
considered the gold standard in evaluating the animal’s response to the
anemia. Reticulocytes are immature red blood cells with increased RNA and
organelles, such as mitochondria and ribosomes. Methodology for reti-
culocyte counts includes vital stains, such as New Methylene Blue, and
flow cytometry [1]. Additionally, peripheral blood smears stained with
Romanowsky stain can be evaluated for polychromasia, which is a reflection
of the reticulocyte response. All polychromatophilic red blood cells are
reticulocytes; however, all reticulocytes are not polychromatophilic [2].
Thus, evaluation of the blood smear for polychromasia should only serve as
a subjective estimate for the presence or absence of a regenerative response
and may, in fact, underestimate the actual reticulocyte response. Calculation
of the absolute reticulocyte count is the preferred method of reticulocyte
enumeration [3]. Multiplying the percentage of aggregate reticulocytes by
the RBC gives the absolute number of circulating reticulocytes. A normal
dog can have up to 1% or about 60,000 reticulocytes/lL of blood. Healthy
cats generally have less than 0.4% or up to 40,000 reticulocytes/lL of blood.
Thus, an absolute value of 60,000 reticulocytes/lL in the dog and an
absolute value of 40,000 reticulocytes/lL in the cat are the minimum values
for indicating a regenerative response. An additional distinction must be
made in cats between aggregate and punctate reticulocytes (Fig. 1). The
aggregate reticulocytes are similar to those observed in dogs and are
a reflection of current bone marrow activity. Aggregate reticulocytes in the
cat mature into punctate reticulocytes, however. Punctate reticulocytes
increase with erythropoiesis, but the increase is delayed and may persist for
3 to 4 weeks after the bone marrow response [4]. A healthy cat may have up
to 17% punctate reticulocytes in circulation. The absolute reticulocyte count
should only include aggregate reticulocytes, because these cells are used to
evaluate the regenerative capability of the bone marrow.
Many factors influence the reticulocyte response, including duration and
severity of anemia, species difference, and age and health status of the animal.
All these factors must be considered in determining the adequacy of response.
Ultimately, the anemia must cause hypoxia at the level of the kidney to
 A.M. Barger / Vet Clin Small Anim 33 (2003) 1207–1222 1209

Fig. 1. New methylene blue–stained blood smear. Aggregate reticulocytes from a cat with
regenerative anemia.

stimulate erythropoietin release, leading to a bone marrow response. It may

take 3 to 5 days before the presence of a marrow response is reflected in the
peripheral blood. Before this, the anemia may appear nonregenerative. In
early blood loss or destruction, erythroid hyperplasia in the marrow precedes
an elevated reticulocyte count. Therefore, bone marrow aspiration can be
beneficial for immediate assessment of the regenerative response.
The red blood cell indices MCV, MCH, and MCHC are used to evaluate
overall red cell size and hemoglobin concentration. These indices can be
beneficial in assessment of anemic patients. The terms macrocytic,
normocytic, and microcytic are used to reflect the MCV and overall cell
size. The terms hypochromic and normochromic refer to the MCH and
MCHC and the overall hemoglobin concentration. Rarely is the term
hyperchromic used. An elevated MCHC or MCH is usually the result of in
vitro or in vivo hemolysis. In addition, the presence of interfering substances,
such as lipemia or Heinz bodies, may significantly elevate these two indices.
Most anemias are normocytic and normochromic. In markedly re-
generative anemias, indices may indicate a macrocytic and hypochromic
anemia (ie, increased MCV, decreased MCHC), reflecting the increased size
and decreased hemoglobin of the reticulocytes. This morphologic classifi-
cation is consistent with a regenerative anemia. Indices are insensitive
indicators of regeneration, however, and may be normal despite the
presence of a regenerative response. A slightly more sensitive indicator is the
combination of an elevated MCV and red cell distribution width (RDW) [5].
Nevertheless, the presence of an elevated absolute reticulocyte count is the
best measure of regeneration. As outlined in Box 1, an elevated MCHC or
1210 A.M. Barger / Vet Clin Small Anim 33 (2003) 1207–1222

Box 1. Interpreting instrument-derived red blood cell indices

Mean corpuscular volume
Macrocytosis (increased mean cell volume)
Reticulocytosis (regenerative anemia)
Acute blood loss (>3 days)
Acute hemolytic anemia (>3 days)
Early iron deficiency in young animals
Hereditary microcytosis of toy and miniature poodles (no
anemia)
Stomatocytosis
Hereditary (Alaskan Malamute, Miniature Schnauzer, Drentse
Patrijshond)
Acquired
Red blood cell agglutination (immune-mediated hemolytic
anemia)
Macrocytosis of feline leukemia virus
Vitamin B12 or folic acid deficiency (unlikely in animals)
Artifact (old blood sample, hypertonic red blood cells in
isotonic or hypotonic fluid)
Numerous large platelets or white blood cells measured as red
blood cells; most frequently observed in severely anemic
cats
Microcytosis (decreased mean cell volume)
Absolute iron deficiency (decreased bone marrow iron stores,
serum ferritin, and serum iron)
Dietary deficiency in puppies and kittens
Chronic blood loss in young and adult animals
Ineffective iron use (increased bone marrow iron and serum
ferritin and decreased serum iron)
Anemia of chronic disease (generally normochromic)
Portal systemic shunts may or may not be associated with
anemia
Hereditary microcytosis (Akita, Shiba Inu)
Familial dyserythropoiesis of English Springer Spaniels
Red blood cell crenation
Overanticoagulated sample
Acute reaction of red blood cells to hypertonic fluid
(hyperglycemia, hypernatremia, azotemia)
Red blood cell fragments or platelets measured as red blood cells
Mean corpuscular hemoglobin concentration
Hyperchromasia (increased mean corpuscular hemoglobin
concentration)
 A.M. Barger / Vet Clin Small Anim 33 (2003) 1207–1222 1211

Hemolysis in vitro or in vivo

Spectrophotometric interference (turbidity/color)
Lipemia
Heinz bodies
White blood cell count greater than 50,000 cells/lL
Icterus (can interfere with spectrophotometric reading of
hemoglobin)
Spherocytes formed by membrane loss
Transfusion with hemoglobin-based oxygen-carrying solution
Hypochromasia (decreased mean corpuscular hemoglobin
concentration)
Reticulocytosis
Acute blood loss for longer than 3 days
Acute hemolytic anemia for longer than 3 days
Early iron deficiency in young animals
Absolute iron deficiency (decreased bone marrow iron stores,
decreased serum ferritin)
Dietary deficiency in puppies and kittens
Chronic blood loss in young and adult animals
Ineffective iron use (increased bone marrow iron and serum
ferritin)
Anemia of chronic disease (usually normochromic)
Copper deficiency
Vitamin B6 deficiency

From Barger A, Grindem C. Analyzing the results of a complete blood cell

count. Vet Med 2000;534–46; with permission.

MCH may indicate intravascular hemolysis if in vitro hemolysis and the

presence of interfering substances are ruled out.
Red blood cell destruction (hemolysis) and loss are causes of regenerative
anemia. Differentiation of these ‘‘categories’’ requires evaluation of other
parameters, including total protein, bilirubin, plasma color, and red blood
cell morphology. A decreased PCV and total protein are often observed in
blood loss anemia with normal bilirubin and plasma color. In contrast, the
total bilirubin may be increased in certain hemolytic anemias, and,
particularly with intravascular hemolysis, hemoglobin-tinted (reddish)
plasma may be observed. The presence of abnormal red cell morphology,
including spherocytes and Heinz bodies, may provide clues as to the cause of
the anemia. Finally, the blood smear must be evaluated for red cell
parasites, such as Babesia sp, Mycoplasma sp (formerly Haemobartonella
sp), and Cytauxzoon sp, which may cause red cell destruction.
Nonregenerative anemias are more common and are the result of
decreased red blood cell production. The morphologic classification of these
1212 A.M. Barger / Vet Clin Small Anim 33 (2003) 1207–1222

anemias is usually normocytic and normochromic or microcytic and

hypochromic, having a count of less than 60,000 reticulocytes/lL and less
than 40,000 reticulocytes/lL in the dog and cat, respectively. Many diseases
can result in a nonregenerative anemia, with the most common cause being
anemia of chronic disease (ACD). This anemia is associated with
inflammatory processes, chronic infections, and disseminated neoplasia. A
combination of mechanisms is implicated in ACD, including decreases in
iron availability, erythrocyte survival, and response to erythropoietin [6].
ACD is typically normocytic and normochromic but may progress to
a microcytic and hypochromic anemia. The PCV usually does not fall below
20% in ACD. Additional causes of normocytic and normochromic
nonregenerative anemia include diseases that infiltrate or replace the
normal architecture of the marrow (eg, myelofibrosis, myelophthisis),
decreased erythropoietin concentrations associated with chronic renal
disease, and infectious diseases that affect red cell maturation (eg, feline
leukemia virus [FeLV], feline immunodeficiency virus [FIV], and Ehrlichia
canis). FeLV subtype C has been also reported to cause pure red cell aplasia
[7]. Many drug toxicities, including estrogen compounds, doxorubicin, and
vincristine (in dogs), result in a nonregenerative anemia [8]. When immune-
mediated destruction is directed at erythroid precursors rather than at
mature red cells or early in the course of hemolytic and blood loss anemias,
a regenerative response is absent. In these instances, doing a bone marrow
aspiration and running serial CBCs to evaluate the PCV are important for
an appropriate interpretation. It must also be emphasized that the
regenerative response that is typical of a hemolytic or destructive anemia
may be dampened or absent in patients having a concurrent ACD. The
patient’s history and physical examination findings along with additional
testing, such as blood chemistry, urinalysis, bone marrow aspiration, and, if
warranted, specific testing for infectious causes, must also be evaluated.
Microcytic anemias are associated with either iron deficiency or
inadequate iron use. Specific diseases in which the MCV may be decreased
include chronic blood loss, portal systemic shunts, and iron deficiency in
young animals or associated with chronic blood loss. Although microvas-
cular dysplasias do not generally have a decreased MCV, if combined with
a portal systemic shunt, they can result in a microcytosis [9]. The MCV and
MCHC are insensitive indicators of changes in red cell size and hemoglobin
content and thus may not detect mild or early changes [10].

Polycythemia
Polycythemia is characterized as an elevated PCV, RBC, and hemoglobin
and may be further classified as relative or absolute. A PCV greater than
60%, except in sighthound breeds, should arouse suspicion of polycythemia.
Relative polycythemia is most commonly encountered in dogs and cats;
their total red cell mass is normal but appears increased as a result of
 A.M. Barger / Vet Clin Small Anim 33 (2003) 1207–1222 1213

reduction in plasma volume or redistribution of the red cell mass.

Physiologic and pathologic causes of relative polycythemia may occur.
Physiologic polycythemia results from the injection of a mass of
concentrated erythrocytes into the circulating blood from the spleen. This
response is caused by epinephrine and is usually transient. A pathologic
process that often leads to a relative polycythemia is dehydration. In this
case, the PCV is increased because of an overall decrease in plasma fluid
volume. The patient’s clinical signs as well as other abnormal test values,
which often include increases in albumin, total protein, blood urea nitrogen,
and creatinine, may help to support this diagnosis.
In absolute polycythemia, there is a true increase in the circulating red
cell mass, which may be primary or secondary. The PCV, RBC, and
hemoglobin are increased without an elevation in the total protein.
Secondary polycythemia is caused by an underlying disease that results in
overproduction of erythropoietin; it is relatively common in dogs and cats.
The elevated concentration of erythropoietin is caused by either a compen-
satory physiologic response of the kidney to tissue hypoxia or an ancillary
source of the hormone, such as a renal carcinoma. Differentials for
secondary polycythemia should include pulmonary disease, cardiac disease,
high altitude or other causes of overall tissue hypoxia, and renal neoplasia.
In these cases, blood gas results should show that the arterial oxygen (PO2) is
low. Primary polycythemia is an uncommon myeloproliferative disease
known as polycythemia vera (PV). These patients have a low normal to
decreased erythropoietin concentration with normal arterial oxygen levels.
Further, the absolute numbers of reticulocytes are not increased in these
patients, their red cell fragility is normal, and Na/K pump seems to be
functional [11] Human patients with PV often have elevated platelets and
white blood cell count (WBC); however, this is an inconsistent finding in
dogs [12]. Causes of secondary polycythemia need to be eliminated first
before a diagnosis of PV can be made (Fig. 2). Bone marrow evaluation is
not beneficial in these patients, because erythroid hyperplasia is commonly
observed for both primary and secondary polycythemia. Ultimately,
a detailed history through a physical examination, chest radiographs,
cardiac evaluation, and laboratory tests may be needed to distinguish
primary and secondary polycythemia.

Red blood cell morphology

Further information can be gained from evaluation of red blood cell
morphology on the peripheral blood smear. Morphologic changes that may
be associated with a regenerative response to anemia include an increased
amount of polychromasia, which is often associated with the presence of
Howell-Jolly bodies and nucleated red blood cells (nRBCs). When present in
the absence of polychromasia, nRBCs may indicate pathologic processes
like myeloproliferative diseases, bone marrow toxicity like lead poisoning,
1214 A.M. Barger / Vet Clin Small Anim 33 (2003) 1207–1222

Fig. 2. Diagnostic approach to polycythemia. Elevated packed cell volume patient is

dehydrated.

and splenic disease or lack of a spleen. Anisocytosis indicates an overall

variation in red cell size; it is most commonly caused by macrocytes or
microcytes in combination with red cells that are normal in size. Macrocytes
are often indicative of reticulocytes, because reticulocytes are larger
immature cells. The presence of increased numbers of microcytes is
commonly associated with iron deficiency. Other differentials for microcytes
and macrocytes are outlined in the list in this article.
Variation in cell shape (poikilocytosis) is also a useful morphologic
change that may assist the clinician with formulating a diagnosis. For
example, certain shape changes are highly suggestive of a particular
pathologic process. The presence of red blood cell fragments or schistocytes
resulting from mechanical trauma to circulating erythrocytes are often
associated with disseminated intravascular coagulation. Spherocytes are
densely stained red blood cells that have lost their central pallor (Fig. 3).
These cells are commonly observed in immune-mediated hemolytic anemia
(IMHA); if present in high numbers, they are almost pathognomic for this
disease. Acanthocytes are red blood cells with multiple irregular surface
projections. Their presence has been associated with underlying liver disease
and with splenic hemangiosarcoma in dogs. The presence of Heinz bodies,
 A.M. Barger / Vet Clin Small Anim 33 (2003) 1207–1222 1215

Fig. 3. Canine peripheral blood smear from a dog with immune-mediated hemolytic anemia.
Numerous spherocytes are observed as indicated by the arrows.

keratocytes, or eccentrocytes indicates oxidative damage to the red cell. Cats

can have significant numbers of Heinz bodies with no clinical significance;
however, increased numbers with anemia may indicate a pathologic process.
Disorders in cats that are commonly associated with an increased incidence
of Heinz body formation include hyperthyroidism, lymphoma, and diabetes
mellitus [13]. Oxidant drugs or other compounds that cause a Heinz body
anemia in cats include acetaminophen, propylene glycol, fish-based diets,
propofol, and onions [14]. Although the hemoglobin of the dog is less
vulnerable to oxidant damage, onions, zinc, naphthalene, and, rarely,
vitamin K can induce Heinz body formation.
Other specific red cell shape changes include echinocytes, commonly
known as crenated red blood cells, which have numerous, short, evenly
spaced surface projections. These cells are usually an artifact but have been
reported in some dogs with lymphoma, glomerulonephritis, and snake
envenomation [15]. Dacryocytes are teardrop-shaped cells and can be
observed with myeloproliferative diseases, myelofibrosis, and hypersplen-
ism. Leptocytes, or target cells, can be observed with iron deficiency anemia.
These cells can result in pseudomacrocytosis; they are thin and appear to be
increased in size, but the cell volume is not increased [2].
Evaluation of the peripheral blood smear is also beneficial for
identification of red blood cell parasites. In the cat, Mycoplasma haemofelis,
Mycoplasma haemominutum, and Cytauxzoon felis may be observed. The
hemotrophic mycoplasmas (M haemofelis and M haemominutum) can occur
1216 A.M. Barger / Vet Clin Small Anim 33 (2003) 1207–1222

as individualized cocci, chains, or ring structures on the surface of the red

blood cell. If there are many parasites on each of the red blood cells and the
cat is severely anemic, M haemofelis infection is suspected. The parasitemia
is often low and undetected by microscopic evaluations, however. It is
recommended that a polymerase chain reaction (PCR), which is specific for
these parasites, be run to determine if these cats are infected. C felis is
a protozoan parasite that causes an often fatal disease in domestic cats,
whereas the disease is usually asymptomatic in wild cats. Parasitized red
blood cells usually contain a single ring-shaped structure or piroplasma-like
organism (Fig. 4). In the dog, red cell parasites that have been reported
include Babesia canis (Fig. 5), Babesia gibsoni, Mycoplasma hemocanis, and
M haemominutum. The latter parasite has only been detected using PCR and
not by microscopic methods.

Leukocytes
Evaluation of the leukocytes involves interpretation of the white blood
cell parameters, including the WBC, differential count, and white blood cell
morphology. An elevated WBC is called a leukocytosis, whereas a decreased
WBC is a leukopenia. A markedly elevated leukocytosis, greater than 70,000
lL in the cat and greater than 65,000 lL in the dog is a poor prognostic
indicator [16,17]. Further evaluation of the leukocytosis or leukopenia in-
volves examination of the differential. A manual differential count is per-
formed by counting 100 to 200 cells on the peripheral blood smear, giving

Fig. 4. Peripheral blood smear from a cat infested with Cytauxzoon felis. Piroplasmic
intracellular organisms are indicated by the arrow.
 A.M. Barger / Vet Clin Small Anim 33 (2003) 1207–1222 1217

Fig. 5. Canine blood smear. Intracellular Babesia canis organisms are indicated by the arrow.
These organisms are often observed as large paired piroplasms.

a percentage of each cell type. This percentage must then be multiplied by the
WBC to give an absolute value before attempting to interpret the results. It is
the absolute numbers rather than the percentages that should be used to
classify the differential as consistent with inflammation, stress, excitement,
hypersensitivity, or neoplasia.

Inflammation
The most common changes associated with inflammation include
a leukocytosis with mature neutrophilia, often with increased numbers of
bands present, which is described as a left shift. If the number of bands is
less than the segmented neutrophils, this is described as a regenerative left
shift. Conversely, if the number of bands is greater than the segmented
neutrophils, this is called a degenerative left shift and is a poor prognostic
indicator. The total WBC is usually elevated in a regenerative left shift. The
neutrophils should also be evaluated for toxic changes. These changes may
include cytoplasmic basophilia, Dohle bodies, azurophilic granules, and
foamy cytoplasm. In severe inflammatory responses, leukopenia can occur
rather than leukocytosis. It is not uncommon to observe a degenerative left
shift in these situations.
The identification of toxic changes within leukocytes can be a valuable
‘‘clue’’ for the clinician when struggling to distinguish a leukopenia of
inflammation from that of decreased production. The finding of toxic
changes strongly supports an inflammatory response, whereas their absence
1218 A.M. Barger / Vet Clin Small Anim 33 (2003) 1207–1222

favors a production problem. A careful evaluation of the patient’s history as

well as measurement of fibrinogen or other acute-phase proteins may be
beneficial in distinguishing a chronic inflammatory leukon from a stress
response. Chronic inflammation often is associated with a mature neutro-
philia, having no or few bands. These leukocyte changes are also seen in
conjunction with a stress response.
The presence of an elevated fibrinogen concentration in conjunction with
toxic changes strongly supports a chronic inflammatory response. The
degree of leukocyte elevation is also important, because these numbers
should not exceed 30,000 leukocytes/lL in stress.

Immune stimulation/lymphocytosis
Persistent antigenic stimulation caused by infectious agents, such as
E canis and certain protozoal organisms, or in response to a vaccination
may result in a significant lymphocytosis. This reactive lymphocytosis can
be difficult to differentiate from chronic lymphocytic leukemia (CLL) or
lymphoma with spillover into the blood. A reactive lymphocytosis is
generally accompanied by the presence of immunocytes or reactive
lymphocytes having deeply basophilic cytoplasm. Further, the lymphocy-
tosis usually disappears with recovery from disease. These features help to
distinguish a reactive lymphocytosis from CLL. The presence of a lympho-
cytosis with immature lymphocytes in the blood, favors a diagnosis of
lymphoma. A complete history, physical examination, and additional
testing (ie, Ehrlichia serology) are also essential components necessary to
define a lymphocytosis.

Stress leukogram
The stress leukogram is mediated by endogenous or exogenous
glucocorticoid release rather than by the epinephrine release associated
with excitement. Characteristic changes include a mature neutrophilia,
occasional hypersegmented neutrophils, lymphopenia, monocytosis (in the
dog), and eosinopenia. The expression of L-selectin is downregulated by
glucocorticoids in certain species, which may play an important role in the
development of the mature neutrophilia [18]. The effects of glucocorticoids
usually last for about 24 hours. With continuous endogenous release or
long-term steroid use, however, the changes may be more sustained,
especially the lymphopenia and eosinopenia. There is often a component of
stress that can be recognized on the leukogram of any patient with an
inflammatory lesion. A characteristic stress leukogram is a common finding
in hyperadrenocorticism.

Excitement
The response to epinephrine is immediate but short-lived. It causes
a transient neutrophilia by shifting cells from the marginal pool into the
 A.M. Barger / Vet Clin Small Anim 33 (2003) 1207–1222 1219

circulating pool. Because the total WBC is a reflection of the numbers of

cells in the circulating pool, a leukocytosis is observed. The leukocytosis is
caused by increases in lymphocytes (lymphocytosis) and mature neutrophils
(neutrophilia). The absence of toxic changes in the neutrophils and presence
of a lymphocytosis help to distinguish this leukocytosis from an in-
flammatory leukocytosis. Another change on the CBC that may support an
epinephrine response is the presence of an elevated PCV (relative
polycythemia, physiologic). The epinephrine response is more common in
young animals, cats, and horses. If a second sample could be taken under
more ‘‘relaxed’’ conditions, these changes would likely resolve.

Hypersensitivity
Eosinophils mediate the hypersensitivity response. Allergic, parasitic, and
paraneoplastic syndromes should be considered as possible causes of
eosinophilia. Depending on the level of the eosinophilia, eosinophilic
leukemia and hypereosinophilic syndrome (HES, persistent eosinophilia of
undefined cause) should also be considered. The absolute numbers of
eosinophils may be quite high ([5000 eosinophils/lL) in these conditions.
All possible causes of eosinophilia should be ruled out before a diagnosis of
eosinophilic leukemia or HES can be made. Neoplasms that have been
associated with eosinophilia as a paraneoplastic response include T-cell
lymphoma and mast cell neoplasia.

Hematopoietic neoplasia
A leukocytosis or leukopenia may be observed with hematopoietic
neoplasias. It is more common for patients with leukemia to present with
a marked leukocytosis. If the patient has an acute leukemia, many immature
cells, or blasts, are observed on the blood smear. There are two broad
categories of acute leukemias: acute lymphoblastic leukemia (ALL) and
acute myeloid leukemias (AML). Circulating blasts, usually in low numbers,
may be also observed with stage V lymphoma. Chronic leukemias can be
more difficult to diagnose but usually have gradually increasing numbers of
differentiated hemopoietic cell in the blood, resulting in a marked
leukocytosis (chronic myelogenous leukemia [CML] and chronic lympho-
cytic leukemia [CLL]), erythrocytosis (PV), or thrombocytosis (essential
thrombocythemia [ET]). CML and CLL can only be diagnosed when no
evidence of underlying inflammation or antigenic stimulation is identified in
the presence of a marked leukocytosis. The absence of reactive lymphocytes
or toxic changes in the neutrophils may also support a diagnosis of chronic
leukemia, because these changes are more commonly associated with
immune stimulation or inflammation, respectively.
Hematopoietic neoplasia can result in a leukopenia, especially if
myelophthisis or myelofibrosis has occurred or if the patient is receiving
chemotherapy. Neutropenia can be a limiting factor for treatment.
1220 A.M. Barger / Vet Clin Small Anim 33 (2003) 1207–1222

Additionally, aleukemic leukemia has been reported [19]. These patients

commonly have a cytopenia of one or more cell lineages, which prompts
a marrow evaluation. The presence of greater than 30% blasts in the bone
marrow aspiration is diagnostic for an acute leukemia, despite the absence
of blasts in the peripheral blood.

Platelets
Platelets are small, round to elongate, cytoplasmic fragments of
megakaryocytic origin. They have fine reddish-purple granules scattered
throughout their cytoplasm and primarily function in hemostasis. The
platelet number, size, and morphology are evaluated as part of the CBC.
Platelet counts can be performed on an automated cell counter, performed
manually via a hemacytometer, or estimated from a peripheral blood smear.
The blood smear should also be evaluated for platelet clumps because they
can falsely decrease the platelet count by all three methods. If platelet
clumps are absent, an estimate of 8 to 20 platelets per
100 oil immersion
field indicates that the numbers are adequate in the dog and cat (1 platelet
20,000/lL or 8–20 platelets per
100 oil immersion field ¼ 160,000–
400,000/lL).
Platelet size can also affect the platelet count via automated methods,
because the larger platelets may be counted with the red blood cells; if they
are too small, the platelets are not counted at all. A platelet estimate from
the blood smear may be beneficial in identifying any discrepancies between
methods. Despite a low platelet count, the presence of large densely stained
platelets or macroplatelets suggests active thrombopoiesis, whereas smaller
platelet may suggest a production problem. Additionally, the mean platelet
volume (MPV) can be determined on automated counters, which is a more
accurate determination of their overall size.

Thrombocytopenia
Thrombocytopenia refers to a true decrease in platelet numbers, which is
the most common platelet abnormality encountered. Thrombocytopenia,
like anemia, may be caused by decreased production, increased destruction,
or sequestration or loss. The presence of giant platelets suggests a re-
generative response from the bone marrow; therefore, if giant platelets are
observed, decreased production is a less likely cause. Additionally, an
elevated MPV can be a good indicator of bone marrow response [20]. A
normal MPV may indicate acute thrombocytopenia or nonregenerative
disorders. Microplatelets with a decreased MPV have been reported in dogs
suspected of having immune-mediated thrombocytopenia.
Destruction of platelets is usually immune mediated; however, infectious
etiologies like Ehrlichia platys and canine distemper virus can cause throm-
bocytopenia via destruction [21]. Other infectious causes may lead to platelet
 A.M. Barger / Vet Clin Small Anim 33 (2003) 1207–1222 1221

consumption by triggering disseminated intravascular coagulation; these

include leptospirosis, infectious canine hepatitis, and salmonellosis [22].
Those causes associated with decreased production of platelets are most
often accompanied by other cytopenias. These include bone marrow
toxicity, myelophthisis, myelofibrosis, and primary bone marrow neoplasia.
Certain infectious causes, including FeLV, FIV, panleukopenia, and
parvoviral infections, result in decreased platelet production and other
cytopenia. Similarly, drugs associated with bone marrow toxicity that may
lead to the development of multiple cytopenias include estrogen, tri-
methoprim sulfa, busulfan, 5-fluorouracil, 6-thioguanine, doxorubicin,
daunomycin, cisplatin, and carboplatin [8].

Thrombocytosis
Thrombocytosis is an increased platelet count and may be reactive or
primary. Reactive thrombocytosis has been reported in various conditions,
including acute or chronic inflammation, iron deficiency, and hyperadreno-
corticism. In dogs and cats, the most common diseases categories associated
with thrombocytosis are neoplasia, gastrointestinal disorders, and endocrine
disorders. Physiologic thrombocytosis may occur as a result of increased
mobilization of platelets from splenic and nonsplenic stores; pulmonary pools
of platelets can be mobilized during mild exercise, whereas splenic pools are
mobilized as part of an epinephrine response. These responses are transient,
and only mild to moderate increases are usually seen. Autonomous
thrombocytosis is a myeloproliferative disorder that occurs as a primary
disorder, ET, or in association with other hematopoietic neoplasias, including
PV and chronic granulocytic leukemia (it also occurs inconsistently with acute
megakaryocytic leukemia). It is not uncommon for platelet counts to be
greater than 1 million/lL of blood in these proliferative disorders. Bone
marrow aspiration is beneficial to differentiate these disorders.

Summary
In conclusion, the CBC can be a powerful diagnostic tool. Appropriate
evaluation of all aspects of the CBC can lead to a specific diagnosis or assist
in ruling out many diseases. To gain the full benefit of the CBC, it must be
used in conjunction with a good history and physical examination as well as
with additional components of the minimum database, which include
a chemistry panel and urinalysis.

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