Megakaryocyte impairment by eptifibatide-induced antibodies causes prolonged thrombocytopenia

摘要

Glycoprotein (GP) llbllla inhibitors are used in the treatment of acute coronary syndromes. Transient immune-mediated acute thrombocytopenia is a recognized side effect of GPllbllla inhibitors. We provide evidence that GPIIbllla inhibitor-induced antibodies can affect megakaryocytes in the presence of eptifibatide. In a patient with acute coronary syndrome, acute thrombocytopenia occurred after a second exposure to eptifibatide 20 days after the initial treatment. Despite the short half-life of eptifibatide (t_(1/2) = 2 hours), thrombocytopenia less than 5 x 10~9/L and gastrointestinal and skin hemorrhage persisted for 4 days. Glycoprotein-specific enzyme-linked immunosorbent assay showed eptifibatide-dependent, GPIIbllla-specific antibodies. Bone marrow examination showed predominance of early megakaryocyte stages, and platelet transfusion resulted in an abrupt platelet count increase. Viability of cultured cord blood-derived megakaryocytes was reduced in the presence of eptifibatide and patient IgG fraction. These findings can be explained by impaired megakaryocytopoiesis complicating anti-GPllbllla antibody-mediated immune thrombocytopenia. This mechanism may also apply to some patients with autoimmune thrombocytopenia.