Autoimmune Hemolytic Anemia

Autoimmune hemolytic anemia (AIHA) is a classic example of type II hypersensitivity, caused by autoantibodies that bind red blood cells (RBC). The autoantibodies can be divided into cold or warm types, depending on the optimum temperature at which they bind, and AIHA can also be classified as either primary or secondary if there is an underlying disease such as neoplasia or infection. Hemolysis results from complement fixation leading to membrane attack complex formation, or phagocytosis mediated by receptors for IgGFc and C3. The pathogenicity of cold autoantibodies depends on their thermal amplitude, and on titer, isotype, and phagocyte activation state for warm antibodies. Multiple genetic and environmental factors contribute to susceptibility. Cold autoantibodies most commonly recognize the I blood group, and warm autoantibodies the Rh complex. Studies of responses to RBC autoantigens indicate that warm antibody production is helper dependent and associated with failure of peripheral self-tolerance mechanisms.