Vol. 19, No.
3 March 1997
Continuing Education Article
Refereed Peer Review
FOCAL POINT
★Mechanisms of anemia in
cats are often multifactorial;
determining the mechanism in a
particular case can be difficult.
KEY FACTS
■ Morphologically abnormal RBCs
are inefficiently removed by the
feline spleen and thus are often
encountered on blood smears.
■ Only aggregate reticulocytes
need to be counted in cats with
moderate to marked anemia; in
cats with mild anemia, punctate
reticulocytes also should be
enumerated.
■ Anemia associated with chronic
disease in cats can develop
within 3 days; the hematocrit can
reach as low as 15%.
■ Feline red blood cells are prone
to oxidative damage and Heinz
body–induced hemolysis.
Evaluation of the
Feline Erythron in
Health and Disease
Kansas State University
Mosette Eibert, DVM
David C. Lewis, BVSc, PhD
T he feline erythron has several unusual features; veterinarians must be
cautious when applying their general knowledge of red blood cell
(RBC) physiology and metabolism to feline patients. This article de-
scribes features that are unique to the feline erythron and explains how they
impact the interpretation of RBC data in cats.
GENERAL REQUIREMENTS
Evaluation of the feline erythron includes quantitative and qualitative assess-
ments. Quantitative data provided by commercial laboratories include the
RBC count, hematocrit (HCT) or packed cell volume (PCV), hemoglobin
concentration, mean corpuscular volume (MCV), mean corpuscular hemo-
globin concentration (MCHC), and RBC distribution width (RDW). Quanti-
tative buffy coat analyzers measure the PCV and hemoglobin concentration,
from which the MCHC can be calculated. Qualitative evaluation of RBCs (via
examination of a blood smear) complements quantitative analysis. Examina-
tion for parasitized cells and for changes in RBC shape, size, and staining qual-
ity may provide valuable diagnostic information. Technicians who evaluate
blood smears should be familiar with feline RBC morphology.
SAMPLE COLLECTION AND HANDLING
Jugular venipuncture enables reliable, rapid collection of an adequate blood
volume for complete analysis. Ethylenediaminetetraacetic acid, or EDTA (the
blood collection tube with the lavender top) is the preferred anticoagulant. To
minimize blood loss from small cats and those that require multiple sampling,
small blood collection tubes (2.0- or 0.5-ml draw) are preferable. Tubes should
be filled to the recommended capacity to ensure the proper blood:anticoagu-
lant ratio. Blood should be gently mixed with anticoagulant.
Dilution of a sample with EDTA due to underfilling causes RBC shrinkage;
the results are spuriously decreased HCT and MCV and increased MCHC.1
Blood smears should be made immediately after venipuncture, using nonanti-
Small Animal The Compendium March 1997

coagulated blood that re- tension and potential oxi-

mains in the needle, and dative damage. Because of
should be air-dried quickly structural differences, feline
(fanning the air with the hemoglobin and RBC mem-
slides works well). This branes are more suscepti-
minimizes drying artifacts, ble to oxidative injury than
primarily crenated RBCs, those of other species.6,7 The
which can resemble acan- greater tendency of feline
thocytes (Figure 1). Refrig- hemoglobin to form Heinz
eration of blood samples is bodies after oxidative injury
advised because prolonged is attributed to the greater
(more than 6 hours) storage number (eight) of reactive
of blood in EDTA at room hemoglobin sulfhydryl groups
temperature causes RBC in cats than in other species
swelling with spurious in- Figure 1—Acanthocytes in a cat with hepatic lipidosis. (less than four) and to the
creases in PCV and MCV Acanthocytes are commonly seen in cats with liver disease. ease with which feline hemo-
and decreases in MCHC.2 Crenation of red blood cells (caused by slow drying of globin dissociates from
®
blood smears) resembles acanthocytes. (Diff-Quik stain, tetramers to dimers.8 In ad-
PHYSIOLOGY original magnification ×100) dition, RBCs that contain
Physiologic differences Heinz bodies persist in the
account for many of the circulation because the fe-
unique clinical features of line spleen does not remove
feline RBC disorders. Feline them efficiently. Heinz bod-
RBCs are smaller than those ies, which are clumps of
of many other species; the oxidized and denatured
average diameter is 5.8 µm, hemoglobin, are evident on
compared with 7 µm for ca- Romanowsky-type stained
nine and 8 µm for human smears (e.g., Diff-Quik ®,
3,4
RBCs. To ensure accurate Wright’s, or Giemsa stain) as
RBC counts, the counting pale, knoblike projections
window of the automated from the RBC membrane or
hematology analyzer must as pale, refractile areas with-
be reset for the appropriate in the RBC (Figure 2). With
RBC size range. Analyzers new methylene blue stain,
set for larger erythrocytes Figure 2—Numerous large Heinz bodies, appearing as Heinz bodies appear as small
(e.g., human and canine) knoblike projections from red blood cells, from a cat with blue inclusions within or
will underestimate the total lymphoma. (Diff-Quik ® stain, original magnification protruding from the RBC
feline RBC count, resulting ×100) (Figure 3).
in erroneous calculations of RBCs of apparently healthy
HCT and RBC indexes. cats may contain Heinz bod-
The small size of feline RBCs and the great size varia- ies, although the life span of these cells may be reduced.9
tion of feline platelets result in overlap between platelet Not all cats with Heinz bodies are anemic, and Heinz
and RBC size.5 Because of this factor and the tendency body–induced hemolytic anemia is more likely if the bod-
of feline platelets to clump in EDTA-anticoagulated ies are large or numerous. The shortened life span of RBCs
blood, automated hematology counters cannot provide that contain Heinz bodies is believed to be caused by bind-
reliable platelet counts in cats; abnormal platelet counts ing of the denatured globin moiety of hemoglobin to
must be verified by blood smear evaluation. Cytological- membrane proteins; this causes loss of membrane integrity,
ly, the small size of feline RBCs must be taken into ac- decreased cell deformability, and cell lysis.9
count—they can make other cells appear relatively large. Feline erythrocytes have several distinct morphologic
Normal feline mature lymphocytes may, for example, be characteristics. Normal feline erythrocytes have mini-
interpreted as reactive or immature if the evaluation mal and inconsistent central pallor (Figure 4). RBCs
principles used in dogs are applied. without central pallor resemble spherocytes and cannot
Erythrocytes are continually exposed to high oxygen be distinguished from the spherocytosis that is evident

DRYING ARTIFACTS ■ PLATELET SIZE VARIATION ■ HEMOLYTIC ANEMIA

The Compendium March 1997 Small Animal

in patients with immune- and HCT are significantly

mediated hemolytic ane- lower in cats than in dogs.
mia. 10 Morphologic RBC The blood volume of cats is
abnormalities are more 50 to 60 ml/kg, compared
common in cats than in with 80 to 90 ml/kg for
other species because of the dogs. The HCT of normal
structural characteristics of adult cats is 30% to 45%,
the feline spleen. This organ compared with 37% to 55%
is considered to be nonsinu- for dogs.7,16 Total RBC mass
soidal because it does not is 20% to 30% lower in
possess a sievelike meshwork cats; therefore, cats may be
of reticulum or an endothe- more likely than dogs to
lial barrier through which develop anemia subsequent
RBCs must cross to reenter to hemorrhage or hemolysis.
the circulation.11 As a result, Figure 3—Two Heinz bodies (blue, small red blood cell The lower RBC mass and
removal of damaged RBCs [RBC] inclusions) and a disintegrating nucleated RBC. shorter RBC life span con-
and RBC inclusions (e.g., (New methylene blue stain, original magnification ×100) tribute to the quicker devel-
Heinz bodies, Howell-Jolly opment of anemia associat-
bodies, and RBC parasites) ed with chronic disease in
by splenic macrophages is cats. The propensity of cats
inefficient; damaged RBCs to develop anemia may be
and RBC inclusions thus are somewhat offset by the low
more frequently detected in affinity of feline hemo-
peripheral blood.11 Howell- globin for oxygen, which
Jolly bodies are nuclear rem- enables cats to deliver oxygen
nants that stain dark blue to tissues more effectively.15
with Romanowsky-type Categorizing anemias as
stains (Figure 5). regenerative or nonregenera-
The biochemistry of eryth- tive is not as straightforward
rocytes in cats differs from in cats as in dogs. In cats,
that of other species. Eryth- multiple mechanisms often
rocytes of all species lack contribute to anemia; in
mitochondria and the meta- Figure 4—Normal feline blood smear, demonstrating minimal addition, the laboratory fea-
bolic capabilities of efficient and inconsistent central pallor of red blood cells (RBCs). tures that distinguish re-
energy (ATP) manufacture Spherocytes are thus difficult to identify in feline blood. Note generative from nonregen-
via the Krebs cycle and ox- the variation in platelet size; some platelets are larger than erative RBC responses are
idative phosphorylation. In- RBCs. Large platelet size and the tendency of feline platelets more subtle.17 Feline bone
stead, they depend on an- to clump preclude accurate counting by automated hematolo- marrow has a greater ten-
aerobic glycolysis for ATP gy analyzers. (Diff-Quik stain, original magnification ×100) dency to retain reticulocytes
®

production. 12 The rate of until they are morphologi-

glucose uptake and utiliza-
tion by feline erythrocytes is lower than that of other
animals.13,14 This may be because feline RBCs do not
require synthesis of 2,3-diphosphoglycerate (2,3-DPG)
from glucose. Feline hemoglobin apparently has an in-
nately low affinity for oxygen and does not rely on 2,3-
DPG for efficient tissue delivery of oxygen.12,15
The apparent frequency with which anemia is seen in
cats is probably related to several unique attributes of
feline erythrocyte physiology. The average life span of
feline RBCs is one of the shortest among domesticated
mammals; approximately 70 days, compared with ap-
proximately 112 days for canine RBCs.3,4 Blood volume
cally mature than does canine
bone marrow.17
Evaluating Romanowsky-stained blood smears for
evidence of polychromasia is an unreliable method of
determining the presence of a RBC regenerative re-
sponse in cats. As in dogs, a regenerative response in
cats with anemia is implied by an increased number of
polychromatophilic (blue-gray staining) RBCs. Howev-
er, only the very youngest feline RBCs are recognized as
polychromatophils via Romanowsky-type stains (these
cells would appear as classic or aggregate reticulocytes
with new methylene blue stain), and these cells consti-
tute only a portion of the immature RBCs in circula-

ROMANOWSKY–TYPE STAINS ■ KREBS CYCLE ■ RBC MASS

Small Animal The Compendium March 1997

tion during a regenerative reticulocytes have single to

response to anemia. Diff- multiple spots of precipitate
Quik ® stains commonly within the RBC and circulate
used for rapid slide process- for approximately 10 days
ing do not allow detection before maturing to normal
of any immature feline erythrocytes.21 Punctate retic-
10,17,18
RBCs. Therefore, al- ulocytes do not stain as poly-
though the presence of nu- chromatophils with Ro-
merous polychromatophilic manowsky-type stains.
cells (3 to 4 per oil immer- There is not always a
sion field) on a Roman- clear distinction between
owsky-stained blood smear aggregate and punctate reti-
from an anemic cat indi- culocytes. This has led to a
cates a regenerative re- third group of feline reticu-
sponse, such a response can- Figure 5—Howell-Jolly body (nuclear remnant) in a blood locytes in some classification
not be excluded by the smear from a normal cat. These bodies are larger and stain schemes. Flow cytometric
®
absence of polychroma- more homogeneously than H. felis organisms. (Diff-Quik counting of thiazole orange-
sia.12,17 stain, original magnification ×100) stained reticulocytes is more
Although reticulocyte sensitive than is manual
counts are the gold standard counting and enables detec-
for distinguishing regenera- tion of aggregate and punc-
tive from nonregenerative tate reticulocytes as distinct
anemia, they are tedious to populations22; however, this
perform and prone to con- technology is not widely
siderable variability, and available. Reporting of re-
their interpretation is more ticulocytes varies among la-
difficult in cats than in boratories; it is essential to
dogs. 19,20 A reticulocyte know which types of reticu-
count is indicated for cats locytes are being counted
that apparently have nonre- and whether aggregate and
generative or inadequately punctate reticulocytes are
regenerative anemia based being differentiated. Most
on Romanowsky-stained laboratories report only the
blood smears. Reticulocyte Figure 6—One aggregate and one punctate reticulocyte from aggregate reticulocytes as a
counts are performed with a cat with hemolytic anemia caused by H. felis infection. percentage. For accurate in-
new methylene blue stain. (New methylene blue stain, original magnification ×100) terpretation, the raw reticu-
An aliquot of EDTA-antico- locyte percentage must be
agulated blood is mixed corrected for the degree of
with an equal amount of 0.5% new methylene blue anemia by calculating the absolute reticulocyte count or
and allowed to incubate for 20 minutes before a blood the corrected reticulocyte percentage as follows:
smear is prepared to determine the percentage of reticu-
locytes per 1000 RBCs. New methylene blue causes Absolute Reticulocyte Count = Reticulocyte
precipitation and staining of RNA and protein vestiges Percentage × RBC Count (RBCs × 106/µl)
present in immature RBCs; these vestiges furnish the
characteristic stippled markings of reticulocytes. Corrected Reticulocyte Percentage = Reticulocyte
Unlike those of other species, reticulocytes in cats are Percentage × (Patient Hematocrit ÷ 37%)
classified into two major types based on the amount of
precipitate. Aggregate, classic, or class I reticulocytes have The reticulocyte production index is not valid in
abundant linear aggregates of precipitate and are the least cats. An absolute aggregate reticulocyte number greater
mature of the circulating reticulocytes. They are recogniz- than 50,000/µl or a corrected aggregate reticulocyte
able as polychromatophils via many Romanowsky-type percentage greater than 0.5 supports regenerative ane-
stains, and they mature to the punctate form of reticulo- mia.7,17 Aggregate reticulocyte counts are appropriate
cyte within 12 hours (Figure 6). Punctate (or class II) when assessing moderate to severe anemia (HCT less

RETICULOCYTE COUNT ■ PROTEIN VESTIGES ■ PUNCTUATE RETICULOCYTES

Small Animal The Compendium March 1997

weeks because of maturation of

30 45 aggregate to punctate forms and
continued bone marrow release of
– 40
punctate reticulocytes.23,24 Because
25 – of their relatively long life span,
– 35
Corrected reticulocyte %

punctate reticulocytes are less

– 30 reliable indicators of current RBC

Hematocrit (%)
20 – Punctate
reticulocytes
– 25 demand.
Hematocrit In cats with mild hemorrhagic
15 – – 20 or hemolytic anemia, however, the
– 15
Aggregate increase in aggregate reticulocytes
10 – reticulocytes
can be mild and transient and a re-
– 10 generative response may be over-
5 – _ 5
looked unless punctate reticulocytes
are enumerated17 (Figure 8).23 Ac-
0 cordingly, only aggregate reticulo-
0
0 2 4 6 8 10 12 14 16 cytes must be counted in cats with
Days moderate or marked anemia (HCT
less than 20%), but both types of
reticulocytes should be evaluated in
Figure 7—Mean corrected reticulocyte percentage and hematocrit from three cats
cats with mild anemia.
subsequent to removal of 45% of blood volume.
CAUSES AND
CHARACTERISTICS OF
35 40 ANEMIA IN CATS
Some of the causes and charac-
– 35 teristics of feline anemia are unique
30 –
to cats (see the box). Others, al-
Corrected reticulocyte %

– 30
25 – though evident in various species,
Hematocrit (%)

Punctate
– 25 reticulocytes
have distinct effects on the feline
20 – erythron.
– 20 Hematocrit
15 – Chronic Disease
– 15
Nonspecific chronic illness and
Aggregate
reticulocytes
10 – – 10 inflammation suppress the ability
of the bone marrow to produce
5 – – 5 RBCs. Various localized or general-
ized infectious, inflammatory, or
0 0 neoplastic diseases can cause or
0 2 4 6 8 10 12 14 16 contribute to anemia in cats with
Days chronic disease. Although the ma-
jor mechanism of anemia associated
Figure 8—Mean corrected reticulocyte percentage and hematocrit from three cats
with chronic disease is seques-
subsequent to removal of 15% of blood volume. tration of iron in bone marrow
macrophages, the rapidity with
which anemia can develop indicates
than 20%) but often underestimate the regenerative re- that reduced RBC life span (by mechanisms that are
sponse in cats with mild anemia (HCT greater than not well understood) makes a significant contri-
20%).8 In cats with moderate to marked anemia caused bution .7,25,26 Anemia associated with chronic disease is
by blood loss, aggregate reticulocytes are released with- nonregenerative and mild to moderate (HCT not less
in 4 to 7 days of the onset of the loss (Figure 7).23 than 15%).25 Unlike dogs, cats can develop anemia
Punctate reticulocyte numbers peak during the ensuing from chronic disease in as little as 3 to 4 days.7,25,26 The
1 to 2 weeks and can be increased for as long as 4 rapid development of anemia associated with chronic

MILD ANEMIA ■ CURRENT RBC DEMAND ■ AGGREGATE RETICULOCYTES

The Compendium March 1997 Small Animal

disease in cats is believed to on the course of the disease and concurrent illness.33,34
Causes and be affected by (1) the shorter Typically, hemolytic anemias have the strongest regen-
Characteristics of life span and increased sus- erative response because the recycling of hemoglobin
Feline Anemia ceptibility to oxidative dam- provides ample substrate for erythropoiesis. However,
age of feline erythrocytes and hemobartonellosis can be peracute or acute, and cats
■ Chronic disease (2) the smaller total RBC presented with severe anemia might have had insuffi-
■ Feline leukemia virus mass of cats. cient time to develop a regenerative response. In addi-
tion, concurrent chronic disease, FIV infection, or
infection
Feline Leukemia Virus FeLV infection may compromise erythropoiesis.
■ Feline Infection Hemolysis caused by H. felis results from splenic se-
immunodeficiency Anemia is common in questration of damaged RBCs or immune-mediated
virus infection cats infected with feline hemolysis.7,33 H. felis organisms are small and appear as
■ Hemobartonellosis leukemia virus (FeLV) and bacilli, cocci (singly or in chains), or ring forms on the
■ Cytauxzoonosis can have a variety of mecha- RBC surface (Figure 9).
nisms.27,28 Anemia associated Feline hemobartonellosis can be difficult to confirm
■ Increased number of
with chronic disease can because organisms are present on the RBCs intermit-
Heinz bodies result from FeLV-induced tently, often in very small numbers, and can resemble
■ Hypophosphatemia opportunistic infections. 27 stain precipitate and Howell-Jolly bodies. Stain precipi-
■ Liver disease FeLV can predispose cats to tate can be distinguished from H. felis organisms be-
■ Chronic renal failure hemolytic anemia related to cause it becomes refractile when the focus of the micro-
■ Congenital disorders immune mechanisms, Heinz scope is changed, whereas H. felis remains basophilic.
body formation, or infection Howell-Jolly bodies tend to be larger and stain more
■ Immune-mediated
with Hemobartonella felis.28 homogeneously than do H. felis organisms. Blood
hemolytic disease Anemia due to bone marrow smears that contain numerous, heavily parasitized
disease in cats infected with RBCs are the exception.33
FeLV can be caused by pure RBC hypoplasia, myelo- Many cats with hemobartonellosis are direct anti-
dysplasia, or hematopoietic neoplasia.28,29 Anemia that globulin test (DAT)–positive, or Coombs’ test–positive,
is nonregenerative but macrocytic is frequently at- even when organisms are not detectable. Organisms
tributable to FeLV infection.28 tend to separate from the RBCs in anticoagulated
blood and are most likely to be detected when blood
Feline Immunodeficiency Virus Infection smears are made from freshly collected, nonanticoagu-
Anemia is uncommon in asymptomatic cats infected lated blood from a peripheral vein (e.g., the lateral
with feline immunodefi- marginal ear vein).3 In light
ciency virus (FIV) but is a of the difficulty of confirm-
frequent finding in clinically ing a diagnosis of hemobar-
ill cats.30,31 Anemia is of vari- tonellosis, empirical treat-
able severity, can be regener- ment with oral doxycycline
ative or nonregenerative, (2.5 to 5.0 mg/kg every 12
and is often accompanied by hours for 21 days) is war-
other cytopenias. 31,32 Ane- ranted if H. felis is suspect-
mia in FIV-infected cats can ed.33,34
be caused by viral suppres-
sion of hematopoietic cells, Cytauxzoonosis
chronic disease due to op- The protozoal organism
portunistic infections, hemo- Cytauxzoon felis is an invari-
bartonellosis, malnutrition, ably fatal cause of hemolytic
or malignancy. anemia and has been report-
Figure 9—H. felis organisms—demonstrating bacilli, cocci, ed in the midwestern and
Hemobartonellosis and ring forms—from a cat with feline leukemia virus in- southeastern United States.35,36
Anemia caused by H. felis fection. Note the two polychromatophilic (blue-gray stain- Bobcats are reservoir hosts
infection varies in severity ing) red blood cells. These cells would appear as aggregate
for C. felis, and ticks are the
reticulocytes if stained with new methylene blue. (Wright’s
and can be regenerative or proposed vector. Clinical
stain, original magnification ×100)
nonregenerative depending signs include depression,

OXIDATIVE DAMAGE ■ VIRAL SUPPRESSION ■ REGENERATIVE RESPONSE

Small Animal
anorexia, fever, pallor, ic-
terus, lymphadenopathy,
and splenomegaly.36 Labora-
tory findings include severe
normocytic–normochromic
nonregenerative anemia,
leukopenia, thrombocyto-
penia, and hyperbilirubi-
nemia. Most affected cats
have 1% to 5% parasitized
RBCs. Organisms are large
and appear as a ring-shaped
or bipolar-shaped organism
with a distinct nucleus and
cytoplasm 35 (Figure 10). Figure 10—C. felis organisms—large, ring-shaped inclu- mended for patients with
Schizonts can be found in sions with visible nuclei and cytoplasm. (Diff-Quik® stain, moderate to severe hypo-
macrophages aspirated from original magnification ×100)
the lymph nodes, spleen,
and bone marrow. There is no definitive treatment, and
death usually occurs within 7 days of diagnosis.
Increased Heinz Bodies
Heinz body hemolytic anemia is usually the result of
exogenous oxidants (e.g., methylene blue, vitamin K,
acetaminophen, lidocaine, benzocaine, DL-methionine,
onions, zinc, or the anesthetic agent propofol).9,37,38
Propylene glycol, formerly used as a humectant in
semimoist foods, also causes Heinz body formation.39
An increased number of Heinz bodies may contribute
to anemia in cats with endogenous illness—most no-
tably diabetes mellitus (especially diabetic ketoacidosis),
lymphoma, and hyperthyroidism—as well as various
other illnesses (e.g., FeLV infection, abscesses, upper
respiratory infections, stomatitis, peritonitis, lower uri-
9,28,40
nary tract disease, and chronic renal failure). Baby formation and hypophosphatemia can play roles in the
food that contains onion powder can cause Heinz body
hemolytic anemia in cats, especially in those with a
propensity toward Heinz body formation because of
preexisting illness.41
Most Heinz bodies in cats are large and readily ap-
parent on Romanowsky-stained blood smears (Figure
2). New methylene blue staining can be used for con-
firmation (Figure 3). Heinz bodies can result in erro-
neously increased hemoglobin concentrations, leading
41
to a spurious increase in the MCHC.
Hypophosphatemia
Moderate to severe hypophosphatemia (serum phos-
phorus less than 1.5 mg/dl) that leads to hemolytic
anemia has been reported subsequent to insulin therapy
in cats with diabetic ketoacidosis and after refeeding of
malnourished cats.42,43 Hypophosphatemia occurs be-
cause phosphorus is obligatory for glycolysis and ATP
LYMPHADENOPATHY ■ SCHIZONTS ■ PHOSPHORUS OVERDOSE
The Compendium March 1997
synthesis, and serum phos-
phorus can be rapidly de-
pleted when nutritional
support is initiated in previ-
ously malnourished pa-
tients. RBC lysis occurs
when phosphorus concen-
trations are insufficient for
ongoing ATP production.
Hemolysis occurs intravas-
cularly, and the HCT can
plummet precipitously.42,43
Intravenous phosphorus
supplementation is recom-
phosphatemia. The recom-
mended starting dosage of
potassium phosphate is 0.01 to 0.03 mmol/kg/hr ad-
ministered in calcium-free solutions, with frequent
monitoring of serum phosphorus concentration and
dose adjustment as necessary. Some hypophos-
phatemic cats require much higher doses of phospho-
rus; it may be more effective to provide one third to
one half of the potassium requirement as potassium
phosphate and the remainder as potassium chloride.
Because the potassium requirement is greater than the
phosphorus requirement, this protocol can result in
phosphorus overdose if phosphorus concentrations are
not monitored closely. Frequent (twice or four times
daily) monitoring of serum phosphorus is imperative to
optimize replacement therapy. Oral phosphorus supple-
mentation (0.5 to 2.0 mmol/kg/day) can be used in
cats with less-severe hypophosphatemia.44 Heinz body
hemolytic anemia that sometimes occurs in cats with
diabetes mellitus.40,42
Liver Disease
Anemia in cats with liver disease can be related to
chronic disease, coagulopathy-induced blood loss, hy-
pophosphatemia, or concurrent bone marrow disease.
Poikilocytes (abnormally shaped RBCs) are common in
cats with liver disease.45 Most of these cells are acantho-
cytes, which are RBCs with 2 to 12 irregularly dis-
tributed blunt projections (Figure 1). Altered mem-
brane lipid composition is the proposed mechanism for
acanthocytosis in cats with liver disease.45 It is not clear
whether the life span of acanthocytes is reduced.
Chronic Renal Failure
Deficient renal production of erythropoietin is the
primary mechanism for the nonregenerative, nor-
Small Animal The Compendium March 1997

mochromic, normocytic shorthair and Siamese cats.

anemia in cats with chronic The heme intermediates
renal failure. Other con- cause brownish discoloration
tributing factors may in- of the teeth and urine,
clude hemorrhage from gas- which fluoresce pinkish red
trointestinal ulceration, iron in ultraviolet light. In addi-
deficiency, Heinz body for- tion, porphyria in domestic
mation, decreased RBC life shorthair cats causes mild
span attributable to altered anemia. In Siamese cats,
RBC membrane phospho- porphyria causes severe re-
lipid composition, and bone generative anemia.48
marrow fibrosis. The ane-
mia is mild to severe and Immune-Mediated
is responsive to exogenous Hemolytic Disease
erythropoietin treatment.46 Figure 11—Red blood cell (RBC) autoagglutination in a cat Primary immune-mediat-
Erythropoietin therapy is with immune-mediated hemolytic anemia secondary to H. ed (DAT- or Coombs’ test–
often recommended for cats felis infection. One drop of RBCs was mixed on a slide positive) hemolytic anemia
with HCTs less than 20%. with two drops of saline, and a coverslip was applied for is rare in cats. Most causes of
The dosage is 100 units/kg microscopic examination. (Original magnification ×20) DAT-positive anemia are
three times per week until secondary, including H. felis
a targeted HCT of 30% to infection, FeLV infection,
35% is attained. The dosage and drug reactions (e.g., to
is then adjusted to maintain propylthiouracil or methi-
the HCT within the refer- mazole).7,33,37,49 Mismatched
ence range. Iron supplemen- blood transfusions result in
tation (50 to 100 mg/cat/day immune-mediated hemoly-
of ferrous sulfate) should be sis of donor RBCs. Neonatal
initiated and hypertension isoerythrolysis is a form of
should be corrected before immune-mediated hemoly-
erythropoietin is given. Ane- sis that occurs in some kit-
mia that is apparently refrac- tens with blood type A after
tory to erthyropoietin treat- ingestion of colostrum from
ment can be caused by iron a queen with blood type B.50
deficiency, gastrointestinal Cold-agglutinin disease,
hemorrhage, Heinz body– Figure 12—Red blood cell stacking (rouleaux) in a cat with which results in necrosis of
induced hemolysis, hemo- inflammatory liver disease. Rouleaux can grossly resemble the extremities due to cold-
bartonellosis, or antierythro- autoagglutination; microscopic evaluation (after blood is induced immune-mediated
poietin antibodies.46 mixed with saline) is necessary to distinguish the two. agglutination of RBCs, is
(Original magnification ×40) rare but has been reported
Congenital Disorders in a cat subsequent to lead
Congenital hemolytic dis- poisoning.51
orders are rare. Erythrocyte pyruvate kinase deficiency Spherocytosis cannot be used as an indicator of
has been recognized as a cause of hemolytic anemia immune-mediated hemolytic anemia in cats (Figure
in Abyssinian cats.47 In Abyssinians, Somalis, and a 4). Autoagglutination (RBC clumping) occasionally
Siamese cat, there have been reports of increased ery- occurs in cats and is diagnostic for immune-mediat-
throcyte osmotic fragility (a test that measures RBC tol- ed hemolytic anemia (Figure 11). Rouleaux forma-
erance to differences in serum osmolarity)3 causing tion (organized stacking of RBCs) may also be evi-
hemolytic crises with macrocytosis, mild regeneration, dent in ill cats (Figure 12). Both can cause a grainy
and splenomegaly.48,49 The cause of increased osmotic gross appearance of blood; they must be differentiat-
fragility in these cats is unclear. Porphyria (which can re- ed by microscopic evaluation of a small drop of
sult from various defects in heme formation producing blood mixed with two drops of 0.9% saline. The
defective hemoglobin synthesis and accumulation of the addition of saline disperses rouleaux but not auto-
intermediates of heme) has been described in domestic agglutination.

ERYTHROPOIETIN THERAPY ■ OSMOTIC FRAGILITY ■ SPHEROCYTOSIS

The Compendium March 1997 Small Animal

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