Warm Antibody Hemolytic Anemia

This disease is characterized by the presence of antibodies directed against IgG and/or C3 that are deposited on the surface of the RBC. It comprises 70 percent of all cases of immune hemolytic anemia. These antibodies react with the RBCs at 37°C. After the antibody-RBC interaction, the RBCs are trapped and destroyed in the spleen.

Patients of any age may be affected, but warm antibody hemolytic anemia is most likely to occur in older adults, women more often than men. Most often it is idiopathic; however, up to 25 percent of affected patients have an underlying disease that affects the immune system such as chronic lymphocytic leukemia, Hodgkin's or non-Hodgkin's lymphoma, or systemic lupus erythematosus (SLE). In adults, the disease is typically relapsing. In young children, it often follows an acute infection or immunizations and is unlikely to recur.

The clinical presentation and course of disease are highly variable depending on the severity of the anemia and how rapidly it develops. Many patients will have a mild anemia with splenomegaly. In this setting, the Coombs' test will be positive for IgG but not C3, and the indirect Coombs' test will be negative. Life-threatening anemia also can occur with hemoglobin levels less than 7 g/dL and a reticulocyte count greater than 30 percent. These patients may have marked splenomegaly, pulmonary edema, and mental status changes. Venous thrombosis also can occur. Patients with severe hemolysis generally have a Coombs' test that is positive for both IgG and C3, and the indirect Coombs' test is also often positive. Rare patients have Evans's syndrome, where there is coexistent immune destruction both of RBCs and platelets by different antibodies.

The treatment of warm antibody hemolytic anemia depends on the degree of anemia that develops and the ability of the patient to hemodynamically tolerate anemia. When there is only mild anemia, no treatment is necessary. When significant hemolysis is present, the first-line treatment is prednisone, 1.0 mg/kg per day. About 75 percent of patients will respond to steroid therapy, but up to one-half of these will relapse after the steroids are tapered. Transfusion of red blood cells is difficult in these patients because they will be impossible to crossmatch. Transfusion is indicated for symptoms of angina, congestive heart failure, mental status changes, orthostasis, or hypoxia. In this setting, the patient is slowly transfused with the best match available; acute transfusion reactions can occur. Splenectomy is the second-choice treatment for patients who fail or cannot tolerate steroids. Immunosuppressive drugs such as azathioprine and cyclophosphamide are used occasionally. Treatment of any underlying immunologic disease also may help control the hemolytic anemia. Death in these patients results from severe anemia that cannot be corrected, immunosuppression, venous thrombosis, or underlying immunologic disease.

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