Michael G. DeGroote School of Medicine, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Transfus Med Rev. 2013 Jul;27(3):137-45. doi: 10.1016/j.tmrv.2013.05.005. Epub 2013 Jul 8.
Drug-induced immune thrombocytopenia (DITP) is a challenging clinical problem that is under-recognized, difficult to diagnose and associated with severe bleeding complications. DITP may be caused by classic drug-dependent platelet antibodies (eg, quinine); haptens (eg, penicillin); fiban-dependent antibodies (eg, tirofiban); monoclonal antibodies (eg, abciximab); autoantibody formation (eg, gold); and immune complex formation (eg, heparin). A thorough clinical history is essential in establishing the diagnosis of DITP and should include exposures to prescription medications, herbal preparations and even certain foods and beverages. Clinical and laboratory criteria have been established to determine the likelihood of a drug being the cause of thrombocytopenia, but these criteria can only be applied retrospectively. The most commonly implicated drugs include quinine, quinidine, trimethoprim/sulfamethoxazole and vancomycin. We propose a practical approach to the diagnosis of the patient with suspected DITP. Key features are: the presence of severe thrombocytopenia (platelet nadir <20×10(9)/L); bleeding complications; onset 5 to 10days after first drug exposure, or within hours of subsequent exposures or after first exposure to fibans or abciximab; and exposure to drugs that have been previously implicated in DITP reactions. Treatment involves stopping the drug(s), administering platelet transfusions or other therapies if bleeding is present and counselling on future drug avoidance. The diagnosis can be confirmed by a positive drug re-challenge, which is often impractical, or by demonstrating drug-dependent platelet reactive antibodies in vitro. Current test methods, which are mostly flow cytometry-based, must show drug-dependence, immunoglobulin binding, platelet specificity and ideally should be reproducible across laboratories. Improved standardization and accessibility of laboratory testing should be a focus of future research.
药物诱导的免疫性血小板减少症(DITP)是一种具有挑战性的临床问题,其认识不足,诊断困难,并与严重出血并发症相关。DITP 可能由经典的药物依赖性血小板抗体(如奎宁)、半抗原(如青霉素)、纤维蛋白依赖性抗体(如替罗非班)、单克隆抗体(如阿昔单抗)、自身抗体形成(如金)和免疫复合物形成(如肝素)引起。建立 DITP 的诊断需要详细的临床病史,包括暴露于处方药、草药制剂甚至某些食物和饮料。已经建立了临床和实验室标准来确定药物是否导致血小板减少症,但这些标准只能回顾性应用。最常涉及的药物包括奎宁、奎尼丁、甲氧苄啶/磺胺甲恶唑和万古霉素。我们提出了一种实用的方法来诊断疑似 DITP 的患者。关键特征是:严重血小板减少症(血小板最低点 <20×10(9)/L);出血并发症;首次药物暴露后 5 至 10 天,或随后暴露或首次暴露于纤维蛋白或阿昔单抗后数小时内发病;暴露于先前与 DITP 反应相关的药物。治疗包括停用药物、如果存在出血则输注血小板或其他治疗方法,并提供有关未来避免药物的咨询。通过药物再激发试验阳性(通常不切实际)或体外证实药物依赖性血小板反应性抗体可确诊。目前的测试方法主要基于流式细胞术,必须显示药物依赖性、免疫球蛋白结合、血小板特异性,理想情况下应在各个实验室之间具有可重复性。未来的研究应重点关注改善实验室检测的标准化和可及性。