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血小板聚集测定法和基因分型方法作为PCI患者个体化抗血小板治疗血小板功能检测的最新证据

Most Recent Evidence Behind Aggregometry and Genotyping Methods as Platelet Function Testing for Tailored Anti-Platelet Treatment Among PCI Patients.

作者信息

Gajda Sylwia N, Kołtowski Łukasz, Tomaniak Mariusz

机构信息

1st Department of Cardiology, Public Central Teaching Hospital, Warszawa, Poland.

出版信息

Adv Clin Exp Med. 2015 Jul-Aug;24(4):687-93. doi: 10.17219/acem/27922.

DOI:10.17219/acem/27922
PMID:26469115
Abstract

Aggregometry and genotyping are methods of platelet function testing, which can be beneficial for high-risk patients undergoing invasive cardiac procedures. An optimal level of platelet reactivity (PR) should be maintained. There are discrepancies between individuals and their response to clopidogrel, accounting for the incidence of poor responders from 5% to 44%. This phenomenon predisposes the patients to increased risk of ischaemic events and thereby overall poorer clinical outcome. Prasugrel and tricagrelor are newer without genetic correlation to their action, however associated with increased bleeding risk. Aggregometry methods assess platelet reactivity at the exact moment of blood sampling. They reflect "phenotype" of the patient and vary after drug administration or dose change. The most popular tests are Light Transmission Aggregometry, Vasodilator-Stimulated Protein, VerifyNow, Multiple Electrode Aggregometry and Thrombelastography. There is proven genetic correlation between some cytochrome enzymes on clopidogrel response. The most widely tested is gene CYP2C19, which produces the enzyme transforming clopidogrel into an active metabolite. The CYP2C19*2 allele carriers have higher PR which can result in more thrombotic events. The manuscript shows the most recent evidence behind platelet function testing. Aggregometry is shown to be beneficial in 5 trials and 1 meta-analysis, while one paper was of different opinion. Ten studies show a positive clinical effect of genotyping on patients' outcome, while one does not support it. The best method of identifying high-risk individuals could be both methods and personalisation of antiplatelet therapy may decrease adverse ischaemic outcomes.

摘要

血小板聚集测定法和基因分型是血小板功能检测的方法,这对接受侵入性心脏手术的高危患者可能有益。应维持最佳的血小板反应性(PR)水平。个体之间对氯吡格雷的反应存在差异,无反应者的发生率在5%至44%之间。这种现象使患者发生缺血性事件的风险增加,从而导致总体临床结局较差。普拉格雷和替格瑞洛是新型药物,其作用与基因无关,但出血风险增加。血小板聚集测定法在采血的精确时刻评估血小板反应性。它们反映患者的“表型”,并在给药或剂量改变后发生变化。最常用的检测方法是光透射聚集测定法、血管扩张剂刺激蛋白、VerifyNow、多电极聚集测定法和血栓弹力图。已证实某些细胞色素酶与氯吡格雷反应之间存在基因相关性。检测最广泛的是CYP2C19基因,它产生将氯吡格雷转化为活性代谢物的酶。CYP2C19*2等位基因携带者的PR较高,这可能导致更多血栓形成事件。该手稿展示了血小板功能检测背后的最新证据。血小板聚集测定法在5项试验和1项荟萃分析中显示有益,而有一篇论文持不同观点。10项研究表明基因分型对患者结局有积极临床效果,而有一项研究不支持这一点。识别高危个体的最佳方法可能是同时采用这两种方法,抗血小板治疗的个体化可能会降低不良缺血性结局。

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