Mechanisms of Complement-Mediated Damage in Hematological Disorders

The complement cascade is an ancient defense system that destroys and eliminates threats to normal homeostasis in the bloodstream and tissues. Although multiple controls keep complement in check to minimize innocent bystander injury to normal cells and tissues, defects in complement regulation due to mutations in, or autoantibodies to, complement control proteins underlie the pathogenesis of several hemolytic diseases including paroxysmal nocturnal hemoglobinuria, and atypical hemolytic uremic syndrome. In autoimmune hemolytic anemias complement plays an important role in erythrocyte destruction mediated by antierythrocyte antibodies. The pathogenic mechanisms of these hemolytic diseases are discussed, with an emphasis on pivotal steps in complement activation.