Autoimmune hemolytic anemia: a history.

Abstract

UTOIMMUNE HEMOLYTIC anemia (AIHA) is an acquired immunoIogic disease in which the patient's red blood cells (RBCs) are selectively attacked and destroyed (hemolyzed) by autoantibodies produced by the patient's own immune system. These patients generally display the common symptoms of anemia: weakness, pallor, fatigue, and jaundice. Less obvious is the frequent occurrence of mild splenomegaly. There are 2 major types of AIHA: cold agglutinin disease (CAD) and warm autoimmune hemolytic anemia (WAIHA), which are differentiated by the optimal temperature of reactivity of the autoantibody. A third type of AIHA is the relatively uncommon, but quite distinct, paroxysmal cold hemoglobinuria (PCH). The pathophysiologic mechanisms differ for the different types of AIHA, depending on autoantibody immunoglobulin class and subclass and the ability of the antibody to activate complement. The degree of RBC hemolysis depends, in part at least, on the autoantibody concentration in the patient's blood and on the abifity of the antibody to activate complement. In CAD, the autoantibodies are immunoglobulin M (IgM) immunoglobulins; in WAIHA, the autoantibodies are IgG immunoglobulins. RBCs coated with IgG autoantibody undergo extravascular destruction, primarily in the spleen, whereas RBCs coated with complement (mediated by IgM and some IgG autoantibodies) can be destroyed either intravascularly or extravascularly. Although it may occur in both the warm and cold types of AIHA, intravascular hemolysis is classically more associated with CAD (and with PCH) ,and leads to increased plasma hemoglobin and hemoglobinuria, resulting in red, brown, or tea-colored plasma and urine. Extravascular destruction of the RBC (classic in WAIHA, but also common in CAD) results in increased bilirubin in the plasma and urine urobilin, resulting in jaundice and dark yellow urine. AIHA is further classified into (1) primary or idiopathic, in which no associated disease is identified, and (2) secondary, associated with collagenvascular disorders such as systemic lupus erythematosus (SLE), lymphomas and leukemias, rheumatoid arthritis, ulcerative colitis, lupoid hepatitis, etc. Whereas both secondary WAIHA and CAD have been associated with SLE, lymphomas, and leukemias, secondary CAD is also known to result from infectious mononucleosis and Mycoplasma pneumoniae infections. PCH, which has historically been associated with syphilis, has more recently been more commonly associated with rubella and other virus infections and may be idiopathic in some cases. The main current treatments for WAIHA are corticosteroids, splenectomy, and immunosuppressive drugs, with a wide variety of therapies employed with varying success in cases resistant to the three approaches. CAD is treated by keeping the patient warm, blood transfusions, and plasmapheresis.