Abstract:
Drug-induced thrombocytopenia (DIT) is a differential diagnosis for consideration when acute thrombocytopenia is encountered in the outpatient or inpatient setting. The mechanism of thrombocytopenia induced by different antiplatelet therapies varies. DIT may occur due to antibody formation following the exposure to a drug, or naturally occurring preexisting antibodies may produce rapid-onset thrombocytopenia when a drug molecule binds to a platelet receptor inducing a conformational change thus rendering it to be an antigen target for naturally occurring antibodies. A 66-year-old female with history of hypertension presented with non-ST elevation myocardial infarction, had drug eluting stent placed in first obtuse marginal artery of left circumflex coronary artery. Started on antiplatelet medications aspirin 81 mg, ticagrelor 90 mg (which was later transitioned to clopidogrel 75 mg), as well as tirofiban 12.5 mg (for 12 hours only). Tirofiban is a GP IIb/IIIa antagonist, other drugs in this class have been documented to induce thrombocytopenia as well, but rates for tirofiban appear to be the highest, the reason is unclear. These antibodies are thought to be either naturally occurring or induced from conformational changes to GP IIb/IIIa binding site after binding to the GP IIb/IIIa receptor, binding of these drugs to the receptor precipitates an epitope much more specific for platelet surface antigens. Tirofiban and clopidogrel/ticagrelor can cause thrombocytopenia, but onset in this case is unusual: acute antibody reaction would be expected within hours, not delayed 30 hours after starting antiplatelet medication, and nonacute reaction would present 1 to 2 weeks out.
摘要:
药物性血小板减少症(DIT)是在门诊或住院患者中遇到急性血小板减少症时考虑的鉴别诊断。不同抗血小板治疗引起血小板减少的机制各不相同。DIT可能由于暴露于药物后抗体形成而发生,当药物分子结合血小板受体诱导构象变化从而使其成为天然存在的抗体的抗原靶标时,或天然存在的预先存在的抗体可产生快速发作的血小板减少症。一位有高血压病史的66岁女性,表现为非ST段抬高型心肌梗死,在左回旋支冠状动脉的第一钝边缘动脉放置药物洗脱支架。开始服用抗血小板药物阿司匹林81毫克,替格瑞洛90mg(后来转为氯吡格雷75mg),以及替罗非班12.5毫克(仅12小时)。替罗非班是GPIIb/IIIa拮抗剂,这类药物中的其他药物也被证明会引起血小板减少症,但是替罗非班的价格似乎是最高的,原因不清楚。这些抗体被认为是天然存在的或在与GPIIb/IIIa受体结合后由GPIIb/IIIa结合位点的构象变化诱导的。这些药物与受体的结合会沉淀出对血小板表面抗原更具特异性的表位。替罗非班和氯吡格雷/替格瑞洛可引起血小板减少症,但是在这种情况下发作是不寻常的:预计急性抗体反应将在数小时内发生,开始抗血小板药物治疗后30小时没有延迟,非急性反应会出现1到2周。