Giugliano RP
TIMI Study Chairman's Office, Brigham and Women's Hospital, Boston, Massachusetts, USA.
J Thromb Thrombolysis. 1998 Jul;5(3):191-202. doi: 10.1023/A:1008887708104.
Over the past decade, several glycoprotein IIb/IIIa receptor antagonists have been developed and tested clinically as adjuncts to coronary intervention and/or treatment of acute coronary syndromes. Thrombocytopenia associated with this class of compounds has been described in most large studies to date and when it occurs in combination with bleeding represents a major safety concern. Cases of thrombocytopenia caused by GP IIb/IIIa antagonists vary in their clinical presentation according to time of onset (following the first dose or delayed), severity (profound, i.e., <20,000 cells/mm(3), or mild), and may or may not be associated with clinically important bleeding. More than one etiology appears responsible for thrombocytopenia associated with GP IIb/IIIa antagonists, including acute, idiosyncratic, as well as delayed immune-mediated mechanisms. Comparison of the incidence of thrombocytopenia across the different agents currently being studied and the one agent commercially available is complicated by varying definitions of thrombocytopenia used to date; different clinical settings in which GP IIb/IIIa antagonists have been studied; use of concomitant medications such as heparin, which itself may cause thrombocytopenia; relatively infrequent occurrence of thrombocytopenia; and the limited number of patients exposed to these agents. Review of the large studies presented and published to date suggests that thrombocytopenia due specifically to GP IIb/IIIa receptor antagonists occurs in less than 5% of treated patients and may vary depending on the type of agent, concomitant therapy, and clinical scenario. Current standard management includes immediate cessation of the GP IIb/IIIa antagonist and, in severe cases, platelet transfusions. In cases with associated hemorrhage, other anticoagulants and antiplatelet agents should be discontinued and possibly reversed. There may be a role for IV IgG and steroids, especially for cases of thrombocytopenia that are immune-mediated; however, further investigations are necessary.
在过去十年中，已经研发出几种糖蛋白IIb/IIIa受体拮抗剂，并作为冠状动脉介入治疗和/或急性冠状动脉综合征治疗的辅助药物进行了临床测试。在大多数大型研究中，均已描述了与这类化合物相关的血小板减少症，当它与出血同时发生时，是一个主要的安全问题。由GP IIb/IIIa拮抗剂引起的血小板减少症病例，其临床表现因发病时间（首次用药后或延迟）、严重程度（严重，即<20,000个细胞/mm³，或轻度）而异，并且可能与具有临床意义的出血有关，也可能无关。与GP IIb/IIIa拮抗剂相关的血小板减少症似乎有多种病因，包括急性、特异质性以及延迟的免疫介导机制。由于目前用于定义血小板减少症的标准各不相同；研究GP IIb/IIIa拮抗剂时所处的临床环境不同；同时使用肝素等可能本身就会导致血小板减少症的伴随药物；血小板减少症相对不常见；以及接触这些药物的患者数量有限，因此比较目前正在研究的不同药物以及一种已上市药物的血小板减少症发生率变得很复杂。对迄今发表的大型研究进行回顾表明，专门由GP IIb/IIIa受体拮抗剂引起的血小板减少症在不到5%的接受治疗的患者中发生，并且可能因药物类型、伴随治疗和临床情况而异。当前的标准处理措施包括立即停用GP IIb/IIIa拮抗剂，在严重情况下进行血小板输注。在伴有出血的病例中，应停用其他抗凝剂和抗血小板药物，并可能进行逆转处理。静脉注射免疫球蛋白和类固醇可能会发挥作用，尤其是对于免疫介导的血小板减少症病例；然而，还需要进一步研究。
