School of Medical Sciences and Health Innovations Research Institute, RMIT University, Melbourne, Australia.
Semin Thromb Hemost. 2012 Mar;38(2):200-12. doi: 10.1055/s-0032-1301417. Epub 2012 Feb 16.
The term resistance has been applied to interindividual variability in platelet reactivity during antiplatelet therapy or to thrombosis despite appropriate therapy. In particular "aspirin resistance" and "clopidogrel resistance" have been the subject of intense investigation for their association with poor cardiovascular outcomes. Several mechanisms have been investigated including resistance arising from poor bioavailability, especially in clopidogrel therapy as resulting from a loss of function variant in hepatic metabolism required for prodrug activation. A limitation of studies linking on-treatment reactivity and clinical outcome is that they have been performed in high-risk patients with recent atherothrombotic disease. On-treatment platelet reactivity correlates with acuity of recent atherothrombosis, and variability in pretreatment platelet function predicts on-treatment platelet function for both aspirin and clopidogrel. It is therefore likely that high on-treatment platelet function at the time of testing may often result from underlying platelet hyperreactivity related to acute atherothrombosis, rather than true pharmacological resistance. The association of high on-treatment platelet reactivity with poor clinical outcomes may therefore be attributed to variability in underlying burden of disease instead of, or in addition to, pharmacological resistance to antiplatelet therapy.
术语“抵抗”已被应用于抗血小板治疗期间血小板反应性的个体间变异性，或用于描述尽管进行了适当的治疗但仍发生血栓形成的情况。特别是“阿司匹林抵抗”和“氯吡格雷抵抗”，由于与不良心血管结局相关，已成为深入研究的对象。已经研究了几种机制，包括由于生物利用度差而产生的抵抗，尤其是在氯吡格雷治疗中，由于肝脏代谢中所需的功能缺失变异，导致前药激活。将治疗中反应性与临床结局联系起来的研究的局限性在于，它们是在近期动脉粥样硬化血栓形成的高危患者中进行的。治疗中血小板反应性与近期动脉粥样硬化血栓形成的严重性相关，治疗前血小板功能的变异性可预测阿司匹林和氯吡格雷的治疗中血小板功能。因此，在检测时高治疗中血小板功能可能常常是由与急性动脉粥样硬化血栓形成相关的潜在血小板高反应性引起的，而不是真正的抗血小板治疗的药物抵抗。高治疗中血小板反应性与不良临床结局相关可能归因于疾病基础负担的变异性，而不是（或除了）抗血小板治疗的药物抵抗。
