Pathogenesis of chronic immune thrombocytopenic purpura

Purpose of review This article summarizes recent insights into the pathophysiology of immune thrombocytopenic purpura, a disorder in which autoantibodies against cell-specific glycoproteins (GPIIb-IIIa, GPIb-IX and others) accelerate platelet destruction. Recent findings Autoantibodies are produced by a limited number of B-cell clones. Platelet antibodies may also impair megakaryocyte development and platelet turnover, thromobopoietin levels are normal or only modestly increased and a compensatory increase in platelet production is not effective in many patients. Patients may show impaired immune regulation manifested by increased proliferation of helper T lymphocytes. Cytotoxic T lymphocytes from patients can lyse platelets in vitro. If cytotoxic T lymphocytes are also capable of perturbing megakaryocyte function, this mechanism may contribute to impaired platelet production. Polymorphisms in the Fc gamma-RIIIa gene may correlate with response to certain forms of therapy and similar genetic approaches may help to identify subsets of patients that differ in their natural history and response to various interventions. Summary Better understanding of autoantibody development, inhibition of thrombopoiesis and Fc gamma receptor and other polymorphisms will assume increased importance in elucidating the pathogenesis and targeting treatment of chronic immune thrombocytopenic purpura.