ESSENTIALS OF DIAGNOSIS
Acquired hemolytic anemia caused by IgG autoantibody.
Spherocytes and reticulocytosis on peripheral blood smear.
Positive antiglobulin (Coombs) test.
Warm autoimmune hemolytic anemia is an acquired disorder in which an IgG autoantibody is formed that binds to a RBC membrane protein and does so most avidly at body temperature (ie, a “warm” autoantibody). The antibody is most commonly directed against a basic component of the Rh system present on RBCs. When IgG antibodies coat the RBC, the Fc portion of the antibody is recognized by macrophages present in the spleen and other portions of the reticuloendothelial system. The interaction between splenic macrophages and the antibody-coated RBC results in removal of RBC membrane and the formation of a spherocyte due to the decrease in surface-to-volume ratio of the surviving RBC. These spherocytic cells have decreased deformability and are unable to squeeze through the 2-mcm fenestrations of splenic sinusoids and become trapped in the red pulp of the spleen. When large amounts of IgG are present on RBCs, complement may be fixed. Direct complement lysis of cells is rare, but the presence of C3b on the surface of RBCs allows Kupffer cells in the liver to participate in the hemolytic process via C3b receptors. The destruction of RBCs in the spleen and liver designates this as extravascular hemolysis. The clinical distinction between extra- and intra-vascular hemolysis is not always straightforward.
Approximately one-half of all cases of autoimmune hemolytic anemia are idiopathic. The disorder may also be seen in association with SLE, other rheumatic disorders, chronic lymphocytic leukemia (CLL), or lymphomas. It must be distinguished from drug-induced hemolytic anemia. When penicillin (or other medications, especially cefotetan, ceftriaxone, and piperacillin) coats the RBC membrane, the autoantibody is directed against the membrane-drug complex. Fludarabine, an antineoplastic, causes autoimmune hemolytic anemia through immunoincompetence: there is defective self- versus non–self-immune surveillance permitting the escape of a B-cell clone, which produces the offending autoantibody.
Autoimmune hemolytic anemia typically produces an anemia of rapid onset that may be life-threatening. Patients complain of fatigue and dyspnea and may present with angina pectoris or heart failure. On examination, jaundice and splenomegaly are usually present.
The anemia is of variable degree but may be very severe, with hematocrit of less than 10%. Reticulocytosis is present, and spherocytes are seen on the peripheral blood smear. In cases of severe hemolysis, the stressed bone marrow may also release nucleated RBCs (eFigure 13–16). As with other hemolytic disorders, the serum indirect bilirubin is increased and the haptoglobin is low. Approximately 10% of patients with autoimmune hemolytic anemia have coincident immune thrombocytopenia (Evans syndrome).
Autoimmune hemolytic anemia, warm antibody type, peripheral blood smear. ...