Pediatric

Hematology
C. Guillermo Couto, DVM,
Diplomate ACVIM
College of Veterinary Medicine
The Ohio State University, Columbus, OH USA
By 810 weeks of age, most healthy pups and kittens
have Hct/PCV and MCV within the reference range for
adults (Figures 1 and 2). Most pups and kittens have slightly
lower serum and plasma protein concentration than the
adults (primarily due to low immunoglobulin concentration).
Although some pups and kittens have slightly higher
lymphocyte counts than adults, leukocyte parameters are
usually within the reference range.1-3 There is a paucity of
information on platelet numbers in pups and kittens.

INTRODUCTION
Hematology is a rapidly growing area in veterinary medicine,
in part due to the recent availability of simple, user-friendly,
bench-top hematology analyzers. Pediatric hematology is an
important area, since some hematologic values (eg, red blood cell
[RBC] parameters) in normal puppies and kittens can be outside
the reference range for the species; there are also a large number
of congenital (and some hereditary) blood disorders manifested
early in life.
This article will review some of the common features of
pediatric complete blood counts (CBCs), and the most common
hematologic and hemostatic abnormalities in pups and kittens.

PEDIATRIC HEMATOLOGIC DISEASES

Pediatric hematologic abnormalities that lead owners
to seek veterinary care are quite common in small animals.
As with all hematologic abnormalities in adults, some are
primary and some are secondary to local or systemic diseases.

THE PEDIATRIC CBC

ANEMIA

To my knowledge, there are no reports of hematologic

findings in outbred, mixed-breed neonatal and young dogs
or cats. Most of the reports are based on information
obtained in colony animals and may not be representative
of the general population seen in practice.
Puppies and kittens are born with higher hematocrit
(Hct) and packed cell volume (PCV) than adults, and also
have higher mean cell volume (MCV). After a few weeks
of age, the Hct/PCV and the MCV decrease (as fetal RBCs
are replaced with adult RBCs and some degree of iron deficiency anemia due to low iron concentration in the
mothers milk develops); (Figures 1 and 2).1,2 Due to the
ongoing hemolysis of fetal RBCs, most pups and kittens display
some evidence of regeneration (4 to 6% reticulocytes).

Anemia is likely the most common hematologic abnormality in pups and kittens, and is defined as a decrease in
the PCV or Hct, the hemoglobin (Hb) concentration, or
the RBC count below reference values for the species. As
discussed above, young pups and kittens have physiological
anemia, so their PCV, Hct, Hb, and RBC count are
expected to be below the adult reference range.4
Anemias are classified as regenerative, nonregenerative, and semi-regenerative, based on the degree of bone
marrow response (Table 1).4 Regenerative anemias are
always due to extramedullary causes, and are the result of
either blood loss or hemolysis; because reticulocytes are
larger than mature RBCs, the anemia is typically macrocytic
and hypochromic. Nonregenerative anemias are normocytic
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Canine Pediatric Care Symposium WSAVA 2005

and normochromic, and can be due to either bone marrow or

extramedullary causes; extramedullary causes are more
common, and include anemia of chronic disease (ACD),
anemia of chronic renal disease (ARD), and endocrine disorders
(extremely uncommon). Bone marrow causes of nonregenerative anemia include aplasia/hypoplasia, myelophthisis,
and myelodysplasia. The semi-regenerative anemias are easy
to diagnose, since the patient has microcytosis, hypochromasia, a mild reticulocyte response, and usually, thrombocytosis;

pink/red plasma and tea-colored urine (hemoglobinemia and

hemoglobinuria), whereas pups and kittens with extravascular
hemolysis (eg, Mycoplasma haemofelis or pyruvate kinase [PK]
deficiency) have yellow plasma and dark yellow urine (hyperbilirubinemia and bilirubinuria).4,5

The principles of diagnosis and therapy of anemia are

beyond the scope of this article; please refer to Couto CG
(2003)4 for additional discussion.

Table 1. Clinical and hematologic classification of anemia

PCV (%)

MCV (fl)

100
90
80

70
60

Regenerative

Semi-Regenerative

Nonregenerative

(macrocytic, hypochromic)

(microcytic, hypochromic)

(normocytic, normochromic)

Blood Loss
Hemolysis

Iron deficiency anemia

Anemia of chronic disease

Anemia of renal disease
Bone marrow disorder
Endocrine anemia
Blood loss/hemolysis
(peracute)

50
40
30
20
0

Birth

12

16

20

24

Age (in weeks)

Hemolytic Anemias

Figure 1. Hematocrit and mean red cell volume in Beagle pups.

PCV (%)

Hemolytic anemias due to RBC enzyme or membrane

defects are relatively common in pups (Table 2); RBC
membrane defects can also result in morphologic erythrocyte changes without anemia (Table 3).4,5 Acquired
hemolytic anemias are rare in pups and kittens, with the
exception of zinc-induced hemolysis after ingestion of
metallic foreign bodies in pups.
Pyruvate kinase deficiency anemia occurs mainly in
Basenjis and Beagles, but it also occurs in the breeds listed
in Table 2.4,5 Pups with PK deficiency anemia may display
clinical signs of anemia early in life (frequently before one
year of age); however, the clinical signs are milder than in
dogs with anemia from other causes due to the right-shift in
the oxyhemoglobin dissociation curve. Prominent
splenomegaly (with or without hepatomegaly) is a common
finding during physical examination. The anemia is moderate to severe (Hct 10 to 25%) and strongly regenerative.
Myelofibrosis and osteosclerosis may be terminal events in
dogs with PK deficiency anemia. A diagnosis can be
obtained by measuring PK activity or by using a genetic test
(polymerase chain reaction [PCR]) in some breeds (Basenji
and West Highland White Terrier).
Phosphofructokinase deficiency anemia occurs in
Springer and American Cocker Spaniels.4,5 This enzyme
deficiency renders RBCs sensitive to alkaline hemolysis.
When dogs exercise or become excited, the respiratory
alkalosis results in a massive intravascular hemolytic crisis.
Hence, clinical signs frequently occur during field work, trials, or visits to the veterinarian, and are acute or peracute;
typically, dogs collapse during exercise and have marked
hemoglobinuria (with or without bilirubinuria). The ane-

MCV (fl)

70
65
60
55

50
45
40
35
30
25
20

0-2

2-4

4-6

6-8

8-9

12-13 12-17

20

30

Weeks
Figure 2. Hematocrit and mean red cell volume in kittens.

iron deficiency anemia (IDA) due to chronic blood loss (eg,

flea infestation or hookworms) is common in pups and kittens. The iron concentration in carnivore milk is low; this
also contributes to the pathogenesis of anemia in weanling
pups and kittens.
Pediatric patients are frequently brought to the veterinary
practice for evaluation of lethargy, pallor, or rapid heart rate.
A distended abdomen may also be obvious and some of the
affected pups and kittens also have severe flea infestation. In
anemic pups and kittens, the color of the urine or plasma may
assist in limiting the number of differential diagnoses. For
example, pups with intravascular hemolysis (eg, phosphofructokinase deficiency [PFK] anemia in Springer Spaniels) have
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Canine Pediatric Care Symposium WSAVA 2005

Iron Deficiency Anemia

Table 2. Hemolytic anemia due to red blood cell enzyme or

membrane defects in pups and kittens

Defect

Breeds
Dog

Pyruvate kinase
(PK) deficiency

Phosphofructokinase
(PFK) deficiency
Glucose 6 phosphate
(G6PD) deficiency
Cytochrome reductase
(Cb5r) deficiency

Iron deficiency anemia (IDA) is common in pups and

kittens.4 As discussed above, carnivore milk contains relatively low concentrations of iron. Therefore, pups and
kittens experience relative iron deficiency. Flea infestation
or GI parasites (primarily hookworms) can compound the iron
deficiency and lead to severe anemia. Hematologic abnormalities include mild to moderate (Hct: 1530%) microcytic
hypochromic anemia, with mild reticulocytosis (2 to 8%
absolute reticulocyte percentage), and in pups, thrombocytosis (platelet count >500,000/l or 500 X 109/L). The red cell
distribution width (RDW) is markedly increased.

Cat

American Eskimo Dog (Toy) Abyssinian

Basenji
Somali
Beagle
Domestic Shorthair
Cairn Terrier
Chihuahua
Dachshund
Miniature Poodle
Pug
West Highland White Terrier
English Springer Spaniel
Cocker Spaniel
Weimaraner
Many breeds

Other Causes of Anemia

Anemia from other causes is relatively rare in pups and
kittens. Anemia of chronic disease (ACD) is a mild (Hct:
2035%) normocytic normochromic anemia associated
with inflammatory or neoplastic diseases, and is rarely
symptomatic. Anemia of renal disease occurs in pups and
kittens with congenital or acquired nephropathies; however, clinical signs of anemia are rarely present. These patients
are usually evaluated for polyuria, polydypsia, weight loss,
and GI signs. Because most patients with chronic renal failure are dehydrated, the anemia is frequently not apparent on
the admitting CBC, but becomes obvious after rehydration.
Bone marrow disorders are extremely rare in pups and
kittens. Bone marrow hypoplasia can occur in kittens
infected with feline leukemia virus (FeLV) or in young dogs
with ehrlichiosis; however, these diseases are uncommon.
Drug-induced bone marrow hypoplasia can occur in kittens
receiving chloramfenicol or griseofulvin, and in pups
receiving estrogen compounds, phenylbutazone, or other
nonsteroidal anti-inflammatory drugs. Endocrine anemias
are extremely rare in young animals.

Many breeds

Porphyrias

Siamese
Domestic Shorthair

mia can be severe (Hct <10%), and is also regenerative;

splenomegaly is common. In contrast with PK deficiency,
there is a left shift in the oxyhemoglobin dissociation curve,
thus increasing affinity for oxygen. Therefore, the magnitude of the clinical signs is higher than expected for the
degree of anemia.
Zinc can induce hemolysis due to direct membrane
damage or oxidative hemoglobin injury.4 In the former, the
hemolysis is intravascular, whereas Heinz body formation
due to hemoglobin oxidation typically results in extravascular hemolysis. Pups with acute onset of hemolytic anemia
associated with gastrointestinal (GI) signs should be evaluated for zinc-induced hemolysis; abdominal radiographs
may reveal a metallic foreign body in the GI tract. The
CBC reveals strongly regenerative anemia, with or without
spherocytes or eccentrocytes; Heinz bodies can also be
observed during examination of the blood smear. Surgical
or endoscopic removal of the foreign body results in resolution of the anemia in hours to days.

COAGULOPATHIES
Congenital hemostatic abnormalities are relatively
common in pups, but rare in kittens. Acquired hemostatic
abnormalities due to ingestion of rodenticides also occur in
pups.6 Pups with congenital or acquired hemostatic abnormalities usually present for evaluation of spontaneous
bleeding, although excessive bleeding after trauma or during/after routine surgical procedures may also occur. In
kittens with hemophilia A, delayed bleeding (ie, 2448
hours) after spay, neuter, or declawing is common.6
Thrombosis as a consequence of hemostatic abnormalities
is extremely rare in pups and kittens.

Table 3. Morphologic red blood cell abnormalities (usually without

anemia) in pups

Red Blood Cell (RBC)

Morphology
Elliptocytosis
Stomatocytosis
Microcytosis

Macrocytosis

Breeds
Mixed Breed
Alaskan Malamute
Schnauzer
Akita
Sharpei
Shiba Inu
Poodle

Canine Pediatric Care Symposium WSAVA 2005

Physiology of Hemostasis for the Clinician

Normally, injury to a blood vessel leads to immediate
vascular changes (eg, vasoconstriction) and to rapid activation of the hemostatic system.6 Exposure of circulating
blood to the subendothelium results in rapid adhesion of
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referred as AT III, a protein synthesized by hepatocytes that

acts as a cofactor for heparin and inhibits the activation of
factors IX, X, and thrombin; and proteins C and S, two vitamin
Kdependent anticoagulants also produced by hepatocytes.
These three factors are some of the natural anticoagulants that
prevent excessive clot formation.

Clinical Manifestations of Bleeding

Patients with hemostatic defects can be easily classified as
having primary or secondary hemostatic abnormalities based
on the physical examination findings.6 Pups with
primary hemostatic defects (ie, platelet disorders, von
Willebrands disease) typically have superficial bleeding;
petechiae, ecchymoses, bleeding from mucosal surfaces
(eg, melena, hematochezia, epistaxis, hematuria), and prolonged bleeding immediately after venipuncture are the
clinical hallmarks. In contrast, pups with secondary hemostatic defects (ie, clotting factor deficiencies) have signs of deep
bleeding, including bleeding into body cavities and joints, and
deep hematomas (most of which are discovered as a lump).

platelets to the affected area; this adhesion is mediated by

adhesive proteins, such as von Willebrand factor (vWF),
fibrinogen, and fibronectin. The platelets then aggregate
and form the primary hemostatic plug, which is short-lived
(seconds) and unstable. The primary hemostatic plug serves
as a framework in which secondary hemostasis occurs.
Activation of the contact phase of the coagulation cascade occurs almost simultaneously with platelet adhesion
and aggregation (Figure 3), and leads to the formation of
fibrin through the intrinsic coagulation cascade. A good
mnemonic is to refer to the intrinsic system as the dime
store coagulation cascade: it is not $12, but $11.98 (for
factors XII, XI, IX, and VIII). The role of the contact phase
of coagulation in vivo is questionable (see below). The secondary hemostatic plug is stable and long-lasting.6
In addition, whenever tissue trauma occurs, the release
of tissue procoagulants (collectively referred to as tissue factor) results in activation of the extrinsic coagulation
cascade, also leading to the formation of fibrin (Figure 3).
Although the intrinsic, extrinsic, and common coagulation
pathways have been well characterized, coagulation does
not necessarily follow these pathways in vivo, in that factors XII and XI do not appear to be needed for the initiation
of coagulation (eg, dogs and cats with factor XII deficiency
do not have spontaneous bleeding tendencies, and some
species of marine mammals lack factor XII).
The stimuli that activate the contact phase of coagulation also activate the fibrinolytic pathway. Fibrinolysis is
extremely important as a safeguard mechanism because it
prevents excessive clot or thrombus formation. The activation of plasminogen into plasmin results not only in the
destruction (lysis) of an existing clot (or thrombus), but
also in interference with the normal clotting mechanisms
(ie, inhibition of platelet aggregation and of clotting factor
activation). Therefore, excessive fibrinolysis usually leads
to spontaneous bleeding.
Other systems that oppose blood coagulation also
become operational once intravascular clotting occurs. The
best-characterized ones include antithrombin (AT), formerly

Intrinsic

Extrinsic

XII XI
IX VIII

TF VIII

Common

APTT
ACT

OSPT
X V
II I

FIBRIN

Figure 3. Coagulation cascade. Factors are in Roman numerals. ACT

(activated coagulation time), APTT (activated partial thromboplastin
time), OSPT (one-stage prothrombin time).

Von Willebrand Disease (vWD) is the most common

inherited bleeding disorder in humans and dogs, but is rare
in cats.6,7 The term von Willebrand syndrome refers to an
acquired vWF deficiency and is extremely rare in dogs and
cats. Von Willebrand disease can be classified into three
types as follows (Table 4): type 1 vWD (low concentration
or activity of vWF), type 2 vWD (low-to-normal concentrations of an abnormal vWF with low concentration of
high-molecular weight multimers), or type 3 vWD (absence
of circulating vWF).
In dogs it can be inherited as an autosomal dominant
trait with incomplete penetrance or, more rarely, as an
autosomal recessive trait. Von Willebrand disease is usually
characterized by primary hemostatic defects (ie, petechiae,
ecchymoses, mucosal bleeding). However, most dogs with
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Canine Pediatric Care Symposium WSAVA 2005

vWD do not bleed spontaneously but rather bleed excessively during or after surgery; excessive bleeding during
teething or estrus can also occur. Most dogs with vWD and
spontaneous bleeding seen at our clinic are brought in for
evaluation of diffuse oropharyngeal bleeding. Perinatal mortality or abortions/stillbirths are common in litters with vWD.6,7
The hemostasis screens are normal in most dogs with
vWD. However, the results of a buccal mucosal bleeding
time (BMBT) or in vitro platelet aggregometry inversely
correlate with the degree of vWF deficiency (ie, the BT is
prolonged if the vWF concentration or activity is low).
Indeed, the BMBT is the most cost-effective method to
screen dogs for vWD, although the results are not foolproof.
A cage-side platelet function analyzer (PFA-100,
Boehringer) is a sensitive method to tentatively diagnose
vWD. A diagnosis of vWD can be confirmed by quantifying vWF in a specialized coagulation laboratory.6,7
Most dogs with type 1 vWD can be treated before surgery
(or during a bleeding episode) with desmopressin acetate
(DDAVP), which causes a massive release of vWF from the
endothelial cells and results in shortening of the BT within 30
minutes of administration in most dogs. A single 1-g/kg dose
of DDAVP (intranasal preparation) given subcutaneously
consistently lessens bleeding in dogs with type 1 vWD.
Desmopressin acetate is not effective in dogs with types 2 or
3 vWD because these dogs either lack or have an abnormal
(ie, nonfunctional) vWF. The administration of fresh frozen
plasma, whole fresh blood, or cryoprecipitate causes the circulating vWF concentration to increase within minutes.

Desmopressin acetate can also be administered to the blood

donor dog one hour before blood is collected to maximize the
yield of vWF. The use of topical hemostatic agents, such as
fibrin, collagen, or methacrylate, is also indicated to control
the local bleeding. As is the case in dogs with other inheritable
disorders, dogs with congenital vWD should not be bred.

Congenital Clotting Factor Deficiencies

Congenital clotting factor deficiencies, as well as the
breeds affected, are listed in Table 5. Congenital factor
deficiencies are relatively common in dogs, but rare in
cats.6-9 Hemophilia A and B are sex-linked traits; the
modes of inheritance of other coagulopathies vary. In
affected animals the severity of the bleeding is usually
inversely proportional to the concentration of the individual clotting factor affected (ie, bleeding is more severe in
association with low factor activity). Clinical signs usually
include spontaneous hematoma formation (which the owners may describe as lumps) and bleeding into body
cavities, as well as signs compatible with fading puppy syndrome and protracted umbilical cord bleeding after birth;
abortions or stillbirths are common in littermates. Petechiae
and ecchymoses are not present in dogs with congenital
clotting factor deficiencies. Cats with hemophilia usually
do not bleed spontaneously, but rather have intra- or postoperative bleeding.
Carriers of the defect may be asymptomatic, but usually
have prolonged clotting times in vitro. Certain factor deficiencies, including factors XII and XI, Fletcher factor

Table 4. Classification of von Willebrand disease in dogs (modified from reference 7)

Class

Concentration of
von Willebrand factor (vWF)

Breeds Affected

Low concentration of vWF

Airedale Terrier
Akita
Corgi
Dachshund
Doberman Pinscher
German Shepherd Dog
Golden Retriever

Low concentration of abnormal vWF

German Shorthaired Pointer

German Wirehaired Pointer

Absence of vWF

FAMILIAL
Chesapeake Bay Retriever
Scottish Terrier
Shetland Sheepdog

Canine Pediatric Care Symposium WSAVA 2005

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Greyhound
Irish Wolfhound
Manchester Terrier
Poodle
Schnauzer
Shetland Sheepdog
Others

SPORADIC
Border Collie
Bull Terrier
Cocker Spaniel
Labrador
Retriever
Pomeranian

(prekallikrein), and high-molecular-weight kininogen, are also

found in otherwise asymptomatic animals (ie, no excessive
bleeding) with markedly prolonged APTTs. However, massive
(and often life-threatening) postoperative bleeding (starting
24 to 36 hours after surgery) is common in dogs with factor XI
deficiency.
Most dogs and cats with congenital coagulopathies are
treated with supportive and transfusion therapies; no other
treatments appear to be beneficial. Like animals with other
congenital defects, dogs and cats with coagulopathies
should not be bred.

REFERENCES
1. Anderson AC, GeeW. Normal blood values in the beagle. Vet Med 1958;
53:135.
2. Anderson L, Wilson R, Hay D. Haematological values in normal cats from
four weeks to one year of age. Res Vet Sci 1971; 12:579.
3. Clinkenbeard KD, Cowell RL, Meinkoth JH, Decker LS, Boudreaux MK,
Rogers KS. The Hematopoietic and Lymphoid Systems. In: Hoskins JD,
ed. Veterinary Pediatrics. Dogs and Cats from Birth to Six Months, 3rd ed.
Philadelphia: WB Saunders Co, 2001; 300-343.
4. Couto CG. Anemia. In: Nelson R, Couto CG, eds. Small Animal Internal
Medicine, 3rd ed. St. Louis: Mosby, 2003; 1156-1169.
5. Giger U. Erythrocyte Phosphofructokinase and Pyruvate Kinase
Deficiencies. In: Feldman BF, Zinkl JG, Jain NC, eds. Schalms Veterinary
Hematology, 5th ed. Philadelphia: Lippincott Williams and Wilkins, 2000;
1020-1025.
6. Couto CG. Disorders of hemostasis. In: Nelson R, Couto CG, eds. Small
Animal Internal Medicine, 3rd ed). St. Louis: Mosby, 2003; 1185-1199.
7. Brooks M. Von Willebrand Disease. In: Feldman BF, Zinkl JG, Jain NC,
eds. Schalms Veterinary Hematology, 5th ed. Philadelphia: Lippincott
Williams and Wilkins, 2000; 509-515.
8. Mansell P. Hemophilia A and B. In: Feldman BF, Zinkl JG, Jain NC, eds.
Schalms Veterinary Hematology, 5th ed. Philadelphia: Lippincott Williams
and Wilkins, 2000; 1026-1029.
9. Dodds WJ. Other Hereditary Coagulopathies. In: Feldman BF, Zinkl JG,
Jain NC, eds. Schalms Veterinary Hematology, 5th ed. Philadelphia:
Lippincott Williams and Wilkins, 2000; 1030-1036.

Table 5. Congenital clotting factor defects (modified from reference 9)

Defect

Breeds
Dog

Factor I
Factor II

Factor VII

Factor VIII
(hemophilia A)
Factor IX
(hemophilia B)
Factor X
Factor XI

Factor XII

Prekallikrein
(Fletcher factor)

Borzoi
St. Bernard
Boxer
English Cocker Spaniel
Otterhound
Beagle
Boxer
Bulldog
Malamute
Miniature Schnauzer
Many breeds, but mainly
German Shepherd Dog
Many Breeds
Cocker Spaniel
Jack Russel Terrier
English Springer Spaniel
Great Pyrenees
Kerry Blue Terrier
German Shorthair Pointer
Miniature Poodle
Standard Poodle
Sharpei
Various Breeds

Cat

Domestic Shorthair
British Shorthair

Many Cats

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Canine Pediatric Care Symposium WSAVA 2005