The pathogenesis of chronic immune thrombocytopenic purpura.

Chronic immune thrombocytopenic purpura (ITP) is an autoimmune disorder in which the patient's immune system reacts with a platelet autoantigen(s) resulting in thrombocytopenia due to immune-mediated platelet destruction and/or suppression of platelet production. Platelet membrane proteins, for reasons that are unclear, become antigenic and stimulate the immune system to produce autoantibodies and cytotoxic T cells. The initial antigenic response probably occurs in the spleen followed by stimulation of other antibody-producing tissues, particularly the bone marrow. Autoantibodies against platelet glycoprotein (GP) IIb-IIIa and/or GPIb-IX are produced by the majority of ITP patients and can be detected using antigen-specific assays. Many patients produce multiple antibodies; this has been attributed to the phenomenon of epitope spreading. Once produced, autoantibody may either bind to platelets, causing their destruction by either phagocytosis or possibly complement activation and lysis, or bind to megakaryocytes, resulting in decreased thrombopoiesis. Evidence for platelet destruction in ITP includes the following: (1) infusion of ITP blood or plasma into normal recipients may result in thrombocytopenia; (2) there is decreased intravascular survival of radiolabeled platelets in most ITP patients; (3) morphologic and in vitro evidence of platelet phagocytosis can be demonstrated; and (4) cytotoxic T cells can induce lysis of autologous platelets. Evidence for suppressed platelet production in ITP includes the following: (1) morphologic studies show megakaryocyte damage in most ITP patients; (2) there is normal or decreased platelet turnover in the majority of patients; (3) in vitro studies show antibody-induced inhibition of megakaryocyte production and maturation; and (4) an increase in the platelet count occurs in many ITP patients receiving treatment with thrombopoietin mimetics. In summary, activation of the immune system by platelet autoantigens in ITP may result in platelet destruction and/or inhibition of platelet production. The importance of each mechanism in the individual patient probably varies.