Case-based approach to anemia (Proceedings) - Veterinary Healthcare


Case-based approach to anemia (Proceedings)


Acute Blood Loss

Diagnosing acute blood loss is simple when an external source of bleeding is present. However, cavity bleeding, gastrointestinal losses, coagulopathies, and chronic blood loss may be more challenging clinical entities. History and physical exam are usually the key elements in identifying a source of acute blood loss. Additional diagnostic testing generally includes minimum database (complete blood count, serum biochemistry panel, and urinalysis) and imaging studies such as radiographs and/or ultrasound to identify the source of bleeding. Platelet counts and coagulation testing should be performed any time hemostatic defects are suspected. Gastrointestinal blood loss should be suspected when external or cavitary bleeding is not identified. Significant gastrointestinal blood loss may occur before signs of melena, hematemesis, or hematochezia are noted.

Treatment of acute blood loss consists of providing hemostasis, administering fluids for volume replacement, and considering blood transfusion if volume support alone is insufficient to provide for tissue oxygen delivery and clinical signs of anemia are present.


In patients presenting with hemolysis, CBC, chemistry, and urinalysis should be run as part of a minimum database. The presence of hemoglobinemia/hemoglobinuria or bilirubinemia/bilirubinuria may suggest intravascular or extravascular hemolysis, respectively. Leukocytosis is frequently noted on the CBC from patients with IMHA and may result from non-specific "gearing up" of the bone marrow, or more likely, from tissue damage secondary to hypoxia and thrombosis. White blood cell counts in excess of 40,000/μl have been associated with a poorer prognosis in dogs with IMHA.1 Platelet counts should also be evaluated. Moderate thrombocytopenias may suggest consumptive coagulopathy or tick-borne illness, while severe thrombocytopenias (<50,000/μl) should prompt consideration of a concurrent immune-mediated thrombocytopenia. A Coombs test is indicated if hemolysis is suspected but autoagglutination is not present. The Coombs test, or direct antiglobulin test, is essentially a test for the presence of antibodies or complement bound to erythrocyte membranes. It is performed by adding anti-dog antibodies (immunoglobulins directed against canine IgG, IgM, or complement) to a sample of the patient's red blood cells. If autoantibodies are present on the patient's blood cells, the antiserum binds to them and cross-linking occurs. Because the end (positive) result of this test is agglutination, the Coombs test need not be run if the patient is already autoagglutinating. Note also that the Coombs test is not highly sensitive. Review of cases seen at our hospital (unpublished data) identified a sensitivity of only 66%, comparable to other reports in the veterinary literature.

A search should also be conducted for possible trigger factors. History taking should include questioning about recent vaccinations or medications. Recent vaccination (ie. within 4 weeks) has been associated with the development of IMHA in retrospective studies.2 Sulfa drugs, penicillins, and cephalosporins may also cause IMHA by acting as haptens, substances that become adsorbed to erythrocyte membranes and subsequently are able to stimulate an immune response. Neoplastic processes such as hemangiosarcoma, lymphoma, leukemia, and histiocytic sarcoma are another common trigger factor, and chest radiographs and abdominal ultrasound are frequently performed to rule out these entities. Testing should also be performed for vector-borne illnesses such as Ehrlichiosis, Babesiosis, Bartonellosis, and Hemoplasmosis.3-5 FeLV and FIV testing should not be overlooked in the cat.

Non-immunologic causes for hemolysis should also be considered. In addition to the oxidative toxins such as onions described above, ingestion of zinc may result in fulminant intravascular hemolysis, hemoglobinuria, multi-organ dysfunction, and DIC. Hereditary diseases such as phosphofrucktokinase deficiency seen in English Springer Spaniels may result in episodic hemolytic anemia, easily confused with IMHA because of its "apparent" response to steroids.

Reticulocyte count should always be performed to assess regenerative response. Hemolytic anemias are typically strongly regenerative, though it may take three days for regenerative response to be noted. The presence of a non-regenerative anemia (absolute reticulocyte count < 60,000/μl) should prompt suspicion of a marrow directed immune-mediated anemia, bone marrow disease, or other forms of decreased production anemia described below.6-8 Immunosuppressive therapies like prednisone ideally should not be initiated until neoplastic and non-immunologic causes of hemolysis have been ruled out, as the use of these drugs may interfere with accurate diagnosis and subsequent therapies. However, in cases where IMHA is strongly suspected and clinical signs are severe, prednisone is typically started pending labwork to avoid excessive delays in therapy.

Decreased Production

An anemia should be considered non-regenerative when the reticulocyte count is less than 60,000/μL (corresponding to a corrected reticulocyte count of less than 1%). However, it should be noted that a regenerative response usually becomes apparent after a minimum of 2-3 days, so acute blood loss or hemolysis may initially appear to be non-regenerative. Once a non-regenerative anemia is identified, bone marrow aspiration is generally indicated. Differentials for decreased production anemias may be grouped according to bone marrow histopathology. Some diseases cause a selective hypoplasia of red cell lines, while others affect all cell lines within the bone marrow (see table 1 above).


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