Megakaryocyte impairment by eptifibatide-induced antibodies causes prolonged thrombocytopenia.
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.
Institut für Immunologie und Transfusionsmedizin, Ernst-Moritz-Arndt Universität, Greifswald, Germany. greinach@uni-greifswald.de
Andreas
A
Greinacher
Birgitt
B
Fuerll
Heike
H
Zinke
Bernd
B
Müllejans
William
W
Krüger
Noemi
N
Michetti
Wolfgang
W
Motz
Hansjörg
H
Schwertz
D054058:Acute Coronary Syndrome / Q000097:blood / Q000276:immunology / Q000628:therapy; D000368:Aged; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001327:Autoimmune Diseases / Q000097:blood / Q000139:chemically induced* / Q000276:immunology* / Q000628:therapy; D000077542:Eptifibatide; D006471:Gastrointestinal Hemorrhage / Q000097:blood / Q000139:chemically induced / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D008297:Male; D008533:Megakaryocytes / Q000276:immunology*; D010455:Peptides / Q000008:administration & dosage / Q000009:adverse effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D010976:Platelet Count; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors / Q000276:immunology*; D017713:Platelet Transfusion / Q000379:methods; D013921:Thrombocytopenia / Q000097:blood / Q000139:chemically induced* / Q000276:immunology* / Q000628:therapy; D034061:Thrombopoiesis / Q000276:immunology; D013997:Time Factors
D001323:Autoantibodies; D007074:Immunoglobulin G; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D000077542:Eptifibatide