Autoimmune Hemolytic Anemia - Causes

Causes

The causes of AIHA are poorly understood. The disease may be primary, or secondary to another underlying illness. The primary illness is idiopathic (the two terms being used synonymously). Idiopathic AIHA accounts for approximately 50% of cases. Secondary AIHA can result from many other illnesses. Warm and cold type AIHA each have their own more common secondary causes. The most common causes of secondary warm-type AIHA include lymphoproliferative disorders (e.g. chronic lymphocytic leukemia, lymphoma) and other autoimmune disorders (e.g. systemic lupus erythematosis, rheumatoid arthritis, scleroderma, ulcerative colitis). Less common causes of warm-type AIHA include neoplasms other than lymphoid, and infection. Secondary cold type AIHA is also primarily caused by lymphoproliferative disorders, but is also commonly caused by infection, especially by mycoplasma, viral pneumonia, infectious mononucleosis and other respiratory infections. Less commonly, it can be caused by concomitant autoimmune disorders.

Drug-induced AIHA, though rare, can be caused by a number of drugs, including α-methyldopa and penicillin. This is a type II immune response in which the drug binds to macromolecules on the surface of the RBCs and acts as an antigen. Antibodies are produced against the RBCs, which leads to complement activation. Complement fragments, such as C3a, C4a and C5a, activate granular leukocytes (e.g. neutrophils), while other components of the system (C6, C7, C8, C9) can either form the membrane attack complex (MAC) or can bind the antibody, aiding phagocytosis by macrophages (C3b). This is one type of "penicillin allergy".