A Megakaryocyte with No Platelets: Anti-platelet Antibodies, Apoptosis, and Platelet Production

Primary immune thrombocytopenia (ITP) and drug-induced thrombocytopenia (DITP) are disorders caused primarily by the presence of anti-platelet auto-antibodies (Abs). Hematologists have traditionally seen thrombocytopenia as the result of increased destruction of Ab-coated platelets by the reticuloendothelial system. While accurate, this approach does not fully account for other laboratory observations. There is increasing evidence suggesting a significant cellular component in the etiology of both ITP and DITP. In ITP, megakaryocytes (Mks) show characteristics consistent with increased apoptosis, which correlates with a reduction in platelet production capacity. Platelet production by Mks is impaired in both the bone marrow of ITP patients and in Mks produced in vitro when treated with ITP or DITP auto-Abs. Recently, it was shown that anti GPIb/IX DITP Abs act directly on Mks and induce apoptosis, hinder differentiation, and prevent platelet production. The origin of pathological megakaryocytic apoptosis is yet to be explored in more detail but current observations imply that there is a direct contribution by anti-platelet Abs. Here we review the evidence for Ab-mediated megakaryocytic damage in ITP and DITP, examine possible molecular mechanisms and consider potential clinical implications.