Megakaryocyte impairment by eptifibatide-induced antibodies causes prolonged thrombocytopenia

Blood. 2009 Aug 6;114(6):1250-3. doi: 10.1182/blood-2009-02-203034. Epub 2009 May 8.

Abstract

Glycoprotein (GP) IIbIIIa inhibitors are used in the treatment of acute coronary syndromes. Transient immune-mediated acute thrombocytopenia is a recognized side effect of GPIIbIIIa inhibitors. We provide evidence that GPIIbIIIa 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, GPIIbIIIa-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-GPIIbIIIa antibody-mediated immune thrombocytopenia. This mechanism may also apply to some patients with autoimmune thrombocytopenia.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / blood
  • Acute Coronary Syndrome / immunology
  • Acute Coronary Syndrome / therapy
  • Aged
  • Autoantibodies / blood
  • Autoantibodies / immunology*
  • Autoimmune Diseases / blood
  • Autoimmune Diseases / chemically induced*
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / therapy
  • Eptifibatide
  • Gastrointestinal Hemorrhage / blood
  • Gastrointestinal Hemorrhage / chemically induced
  • Gastrointestinal Hemorrhage / immunology
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology*
  • Male
  • Megakaryocytes / immunology*
  • Peptides / administration & dosage
  • Peptides / adverse effects*
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / adverse effects*
  • Platelet Count
  • Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors
  • Platelet Glycoprotein GPIIb-IIIa Complex / immunology*
  • Platelet Transfusion / methods
  • Thrombocytopenia / blood
  • Thrombocytopenia / chemically induced*
  • Thrombocytopenia / immunology*
  • Thrombocytopenia / therapy
  • Thrombopoiesis / immunology
  • Time Factors

Substances

  • Autoantibodies
  • Immunoglobulin G
  • Peptides
  • Platelet Aggregation Inhibitors
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Eptifibatide