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CHAPTER 82 Anemia 1349
presence of Ig coating on the RBCs indicates immune- spherocytes in the blood smear of a dog with anemia is
mediated hemolysis. A positive Coombs test result should be highly suggestive but not diagnostic of IHA. Spherocytes are
VetBooks.ir interpreted with caution, however, because certain drugs and difficult to identify in cats. Macroagglutination or microag-
glutination can also be detected in these patients (see Fig.
hemoparasites can induce the formation of antibodies that
bind to the RBCs, thus causing secondary immune hemoly-
The typical patient with IHA is a middle-aged, female,
sis (e.g., cats with mycoplasmosis or dogs with babesiosis). 82.6).
The administration of corticosteroids may also result in spayed Cocker Spaniel, Springer Spaniel, or small-breed dog,
decreased binding of Ig molecules to the surface of the RBC although there appears to be an increasing prevalence of IHA
thus resulting in false-negative results. Direct Coombs tests and other immune-mediated cytopenias in Golden Retriev-
are usually not necessary in animals with autoagglutination ers. Clinical signs in dogs with IHA include depression of
because this phenomenon indicates the presence of Ig on the acute (or peracute) onset, exercise intolerance, and pallor or
surface of the RBCs (i.e., biologic Coombs test). Cryoagglu- jaundice, occasionally accompanied by vomiting or abdomi-
tination (i.e., the agglutination of RBCs if the blood sample nal pain. Physical examination findings usually consist of
is refrigerated for 6-8 hours) occurs in a large proportion of pallor or jaundice, petechiae and ecchymoses if immune
cats with mycoplasmosis and is usually associated with an thrombocytopenia is also present, splenomegaly, and a heart
IgM coating on the RBCs; also, more than 50% of cats with murmur. As noted, jaundice can be absent in dogs with IHA.
mycoplasmosis have a positive direct Coombs test. A subset of dogs with acute (or peracute) IHA with icterus
If a causative agent cannot be identified (e.g., RBC para- and usually autoagglutination shows clinical deterioration
site, drug, pennies in the stomach), the patient should be within hours or days of admission because of multifocal
treated for primary or idiopathic IHA while further test thromboembolic disease or lack of response to conventional
results by, for example, serologic tests or polymerase chain therapy. I treat these dogs more aggressively than the typical
reaction (PCR) assay for hemoparasites are pending. As dog with IHA (see later).
noted, primary IHA is considerably more common in dogs Hematologic findings in dogs with IHA typically include
than in cats; thus every effort should be made to identify a strongly regenerative anemia, leukocytosis from neutro-
cause of hemolysis in cats, such as drugs or hemoparasites. philia with a left shift and monocytosis, increased numbers
For a more detailed discussion of IHA, please see the Immu- of nucleated RBCs, polychromasia, and spherocytosis. The
nology section. serum (or plasma) protein concentration is usually normal
Hemolytic anemias not associated with immune destruc- to increased, and hemoglobinemia or bilirubinemia may be
tion of the RBCs are treated by removal of the cause (e.g., present (i.e., pink or yellow plasma). As noted, autoagglu-
drug, infectious agent, gastric foreign body) and supportive tination is prominent in some dogs. Thrombocytopenia is
therapy. Corticosteroids (see later) can be administered to also present in dogs with Evans syndrome or DIC. Dogs
suppress MPS activity while the causative agent is being with intravascular hemolysis frequently have hemoglobin-
eliminated, although this is not always beneficial. Doxycy- uria (i.e., urine dipstick positive for blood and no RBCs in
cline (10 mg/kg orally [PO] q24h for 21-42 days) usually the sediment), and those with extravascular hemolysis have
results in the resolution of signs in dogs and cats with myco- bilirubinuria.
plasmosis. In dogs with babesiosis, the treatment of choice The presence of polychromasia with autoagglutination
depends on the specific organism (see Chapter 98). and spherocytosis in a clinically ill dog with anemia of acute
Immune-mediated hemolytic anemia onset is almost pathognomonic of IHA, with the exception
IHA constitutes the most common form of hemolysis in of Pitbulls with B. gibsoni infection that present with similar
dogs in most of the continental United States; this is not findings. In these cases, a direct Coombs test is usually
likely the case in areas endemic for vector borne diseases. not necessary to confirm the diagnosis. In dogs without
Although two pathogenetic categories of hemolytic anemia some of these physical examination and hematologic find-
are recognized—primary, or idiopathic, and secondary— ings, a direct Coombs test should be performed to detect
most cases of IHA in dogs in our clinic are primary; that is, Ig adsorbed to the RBC membrane. As noted, in Pitbulls,
a cause cannot be found after exhaustive clinical and clini- evaluation of capillary blood in a Diff-Quik–stained slide or
copathologic evaluation. The immune-mediated destruction PCR assay is mandatory to exclude B. gibsoni infection (see
of RBCs can occur in association with drug administration Fig. 82.5).
(e.g., β-lactam antibiotics, barbiturates) or vaccination, but The direct Coombs test is negative in approximately
the latter has not been conclusively demonstrated. With the 10% to 30% of dogs with IHA, although they still tend to
exception of the immune hemolysis secondary to hemopara- respond to immunosuppressive therapy (see later). In these
sitism, IHA is rare in cats, although its prevalence is higher cases enough Ig or complement molecules may be bound to
than in the past. The clinical course in dogs is typically acute, the RBC membrane to induce the MPS to stimulate phago-
but peracute presentations are also common. cytosis but not enough to result in a positive Coombs test.
In IHA, the RBCs become coated mainly with IgG, which In humans, hemolysis can occur with approximately 20 to
leads to the early removal of the coated cells by the MPS, 30 molecules of Ig bound to the RBC, whereas the direct
generally in the spleen and liver. As a consequence, sphero- Coombs test can only detect more than 200 to 300 mol-
cytes are generated (see Fig. 82.4); therefore the presence of ecules of Ig/cell. In some patients, prior administration of