Peter K, Straub A, Kohler B, Volkmann M, Schwarz M, Kübler W, Bode C
Internal Medicine III, University of Freiburg, Germany.
Am J Cardiol. 1999 Sep 1;84(5):519-24. doi: 10.1016/s0002-9149(99)00370-7.
The blockade of the platelet integrin glycoprotein (GP) IIb/IIIa has proved to be an effective antiplatelet therapy. Profound thrombocytopenia has repeatedly been described as an adverse effect in patients treated with GP IIb/IIIa inhibitors, but its mechanism has not been elucidated yet. With use of flow cytometry, the activation status of platelets was monitored in 26 patients presenting with acute myocardial infarction who were treated with the GP IIb/IIIa inhibitor abciximab alone or in combination with the fibrinolytic agent reteplase. Fibrinogen and PAC-1 (a GP IIb/IIIa activation-specific monoclonal antibody) binding, as well as P-selectin expression on unstimulated platelets were constant in 25 patients throughout a follow-up of 7 days. In 1 patient (D.F.), the percentage of platelet-binding fibrinogen increased from 2.2% to 17.8%, for PAC-1 from 2.8% to 13.2%, and for P-selectin expression from 10.2% to 58.3% 10 minutes after the start of treatment. Furthermore, D.F. had a decrease in single platelet count in ethylenediaminetetraacetic acid-, citrate-, and heparin-anticoagulated and native blood. Blood films revealed platelet aggregates. In vitro testing of D.F.'s blood 2 and 4 weeks after initial admission demonstrated a reinduction of fibrinogen and PAC-1 binding to platelets, an increase of P-selectin expression, and formation of platelet aggregates following exposition of platelets to abciximab in vitro. In summary, this report describes the induction of platelet activation by a GP IIb/IIIa inhibitor in vivo and reinduction in vitro in direct association with thrombocytopenia. Platelet activation by GP IIb/IIIa inhibitors may be one potential mechanism for GP IIb/IIIa inhibitor-induced thrombocytopenia.
血小板整合素糖蛋白（GP）IIb/IIIa的阻断已被证明是一种有效的抗血小板治疗方法。严重血小板减少症反复被描述为接受GP IIb/IIIa抑制剂治疗患者的一种不良反应，但其机制尚未阐明。通过流式细胞术，对26例急性心肌梗死患者的血小板活化状态进行了监测，这些患者单独使用GP IIb/IIIa抑制剂阿昔单抗或与纤溶药物瑞替普酶联合使用。在25例患者的7天随访期间，未刺激血小板上的纤维蛋白原和PAC-1（一种GP IIb/IIIa活化特异性单克隆抗体）结合以及P-选择素表达保持恒定。在1例患者（D.F.）中，治疗开始10分钟后，血小板结合纤维蛋白原的百分比从2.2%增加到17.8%，PAC-1从2.8%增加到13.2%，P-选择素表达从10.2%增加到58.3%。此外，D.F.在乙二胺四乙酸、柠檬酸盐和肝素抗凝及未抗凝血液中的单个血小板计数减少。血涂片显示有血小板聚集。首次入院2周和4周后对D.F.的血液进行体外检测发现，血小板暴露于阿昔单抗后，纤维蛋白原和PAC-1与血小板的结合再次诱导，P-选择素表达增加，并且形成了血小板聚集。总之，本报告描述了GP IIb/IIIa抑制剂在体内诱导血小板活化以及在体外再次诱导，这与血小板减少症直接相关。GP IIb/IIIa抑制剂引起的血小板活化可能是GP IIb/IIIa抑制剂诱导血小板减少症的一种潜在机制。
