In autoimmune hemolytic anemias, red cells coated with IgG autoantibodies against a cell-surface antigen are rapidly cleared from the circulation by uptake by Fc receptor-bearing macrophages in the fixed mononuclear phagocytic system (left panel). Red cells coated with IgM autoantibodies fix C3 and are cleared by CR1- and CR3-bearing macrophages in the fixed mononuclear phagocytic system (not shown). Uptake and clearance by these mechanisms occurs mainly in the spleen. The binding of certain rare autoantibodies that fix complement extremely efficiently causes the formation of the membrane-attack complex on the red cells, leading to intravascular hemolysis (right panel).