Autoimmune hemolytic anemias and paroxysmal nocturnal hemoglobinuria

The hallmark of the autoimmune hemolytic anemias (AIHAs) and paroxysmal nocturnal hemoglobinuria (PNH) is shortened red blood cell survival. Although AIHA and PNH share the critical feature of shortened red cell survival, the mechanisms underlying this characteristic differ significantly between the two diseases. In the case of AIHA, autoantibodies directed against the patient’s own red blood cells lead to accelerated red cell destruction. In PNH, lack of surface complement-regulatory proteins as well as the loss of other surface proteins, leads to exquisite sensitivity of the red cells to complement-mediated lysis. The AIHAs are classified by characteristics of the responsible autoantibodies and their clinical settings (Table 12.1). Serologic differences in optimal temperature of reactivity allow for the differentiation of warm AIHA from cold AIHA; these broad divisions correlate with responsiveness to specific therapy and prognosis. Both warm and cold AIHAs can be further characterized as either a primary, idiopathic autoimmune phenomenon or a secondary process associated with an underlying clinical condition; this information also provides guidance on themost appropriate therapeutic approach. In contrast, PNHoccurs in the context of a somatic genemutation and somecomponent of bone marrowdysfunction.This somaticmutation,which results indecreased glycosylphosphotidylinositol anchored proteins, ultimately leads to increased sensitivity to complement with effects of intravascular hemolysis and increased risk of thrombosis.