The pathogenesis of immune thrombocytopenic purpura

Abstract

Chronic idiopathic thrombocytopenic purpura (ITP) is a human disease manifested by destructive thrombocytopenia due to a circulating antiplatelet antibody. The antibody is of IgG type and is produced primarily in the spleen and bone marrow. After binding of the antibody to a platelet-associated antigen, phagocytosis is triggered either via the Fc portion of the attached antibody or as a consequence of fixation of the third component of complement (C3). The spleen is the prime area of platelet destruction due to its unique milieu. The large intrasplenic platelet pool is subjected to high local antiplatelet antibody concentrations in an environment teeming with phagocytic cells. In addition, the stagnant blood-flow characteristics of the spleen allow ample time for antibody sensitization and phagocytosis. Similar circumstances may occur in the bone marrow. In patients with "severe" disease and high antibody titers, the liver also becomes an important area of platelet destruction. The nature of the platelet-associated antigen is presently unknown but may differ from patient to patient. A pathogenetic model is proposed on the basis of presently available data.