Bennett C L, Connors J M, Carwile J M, Moake J L, Bell W R, Tarantolo S R, McCarthy L J, Sarode R, Hatfield A J, Feldman M D, Davidson C J, Tsai H M
Veterans Affairs Chicago Healthcare System, Department of Medicine, the Robert H. Lurie Comprehensive Cancer Center, Northwestern University, IL 60611, USA.
N Engl J Med. 2000 Jun 15;342(24):1773-7. doi: 10.1056/NEJM200006153422402.
The antiplatelet drug clopidogrel is a new thienopyridine derivative whose mechanism of action and chemical structure are similar to those of ticlopidine. The estimated incidence of ticlopidine-associated thrombotic thrombocytopenic purpura is 1 per 1600 to 5000 patients treated, whereas no clopidogrel-associated cases were observed among 20,000 closely monitored patients treated in phase 3 clinical trials and cohort studies. Because of the association between ticlopidine use and thrombotic thrombocytopenic purpura and other adverse effects, clopidogrel has largely replaced ticlopidine in clinical practice. More than 3 million patients have received clopidogrel. We report the clinical and laboratory findings in 11 patients in whom thrombotic thrombocytopenic purpura developed during or soon after treatment with clopidogrel.
The 11 patients were identified by active surveillance by the medical directors of blood banks (3 patients), hematologists (6), and the manufacturer of clopidogrel (2).
Ten of the 11 patients received clopidogrel for 14 days or less before the onset of thrombotic thrombocytopenic purpura. Although 10 of the 11 patients had a response to plasma exchange, 2 required 20 or more exchanges before clinical improvement occurred, and 2 had relapses while not receiving clopidogrel. One patient died despite undergoing plasma exchange soon after diagnosis.
Thrombotic thrombocytopenic purpura can occur after the initiation of clopidogrel therapy, often within the first two weeks of treatment. Physicians should be aware of the possibility of this syndrome when initiating clopidogrel treatment.
抗血小板药物氯吡格雷是一种新型噻吩并吡啶衍生物，其作用机制和化学结构与噻氯匹定相似。据估计，接受噻氯匹定治疗的患者中，血栓性血小板减少性紫癜的发生率为1/1600至1/5000，而在3期临床试验和队列研究中，对20000名密切监测的接受氯吡格雷治疗的患者未观察到相关病例。由于噻氯匹定的使用与血栓性血小板减少性紫癜及其他不良反应有关，氯吡格雷在临床实践中已基本取代了噻氯匹定。已有超过300万患者接受了氯吡格雷治疗。我们报告了11例在氯吡格雷治疗期间或治疗后不久发生血栓性血小板减少性紫癜的患者的临床和实验室检查结果。
通过血库医学主任（3例）、血液科医生（6例）和氯吡格雷制造商（2例）的主动监测确定了这11例患者。
11例患者中有10例在血栓性血小板减少性紫癜发作前接受氯吡格雷治疗14天或更短时间。虽然11例患者中有10例对血浆置换有反应，但2例患者在临床改善前需要进行20次或更多次置换，2例患者在未接受氯吡格雷治疗时复发。1例患者尽管在诊断后不久接受了血浆置换仍死亡。
氯吡格雷治疗开始后可发生血栓性血小板减少性紫癜，通常在治疗的前两周内。医生在开始氯吡格雷治疗时应意识到这种综合征的可能性。
