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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
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