Farag Mohamed, Gorog Diana A
Postgraduate Medical School, University of Hertfordshire, Hertfordshire. United Kingdom.
Imperial College, London. United Kingdom.
Curr Pharm Des. 2017;23(9):1315-1327. doi: 10.2174/1381612823666170126160359.
Whilst there exist general guidelines regarding administration of antiplatelet therapy to prevent thrombotic events in patients with cardiovascular disease, the optimal therapy for a particular individuals in particular settings remains unclear. For patients with acute coronary syndrome (ACS) or those undergoing percutaneous coronary intervention (PCI), the use of potent antiplatelet agent combinations is recommended. However, some patients continue to have thrombotic events or experience bleeding events, which have been linked to the widely known variability in individual response to antiplatelet therapy, particularly to clopidogrel. Platelet function tests (PFTs) have been used in an attempt to predict ongoing thrombotic risk and to monitor the response to antiplatelet drugs. Although the cause of both thrombotic and bleeding events is multifactorial in origin, the observation that enhanced platelet reactivity is associated with recurrent thrombosis and reduced platelet reactivity with bleeding has raised hopes of identifying those at risk through the use of PFTs. Consequently, there was initial enthusiasm for the use of PFTs to guide individualized antiplatelet therapy. Few studies have been conducted, but the alteration of treatment based on the results of PFTs has not been shown to influence outcomes. Inherent limitations of the studies utilizing PFTs may indeed have contributed to the failure of this approach. Further, there are important limitations to the relevance of currently available PFTs to the in vivo situation. Refinement of existing techniques to allow the use of native blood, high shear, use of a global stimulus instead of individual agonists, assessment of thrombin generation by activated platelets, and assessment of fibrinolytic potential, should be considered to make these tests more physiological. Perhaps the results of PFTs need to be considered in combination with other prognostic factors in a more complex prediction model. The present manuscript provides an overview on the role of and value of available PFTs in contemporary clinical practice, with particular focus on possible individualized antiplatelet regimens in high risk patients.
虽然存在关于抗血小板治疗以预防心血管疾病患者血栓形成事件的一般指南,但特定个体在特定情况下的最佳治疗方法仍不明确。对于急性冠状动脉综合征(ACS)患者或接受经皮冠状动脉介入治疗(PCI)的患者,建议使用强效抗血小板药物联合治疗。然而,一些患者仍会发生血栓形成事件或出血事件,这与众所周知的个体对抗血小板治疗,尤其是对氯吡格雷的反应变异性有关。血小板功能测试(PFTs)已被用于预测持续的血栓形成风险并监测对抗血小板药物的反应。尽管血栓形成和出血事件的原因都是多因素的,但增强的血小板反应性与复发性血栓形成相关,而血小板反应性降低与出血相关这一观察结果,引发了通过使用PFTs识别高危人群的希望。因此,最初人们对使用PFTs指导个体化抗血小板治疗充满热情。进行的研究很少,但基于PFTs结果改变治疗方法尚未显示会影响治疗结果。利用PFTs的研究存在的固有局限性可能确实导致了这种方法的失败。此外,目前可用的PFTs与体内情况的相关性存在重要局限性。应考虑改进现有技术,以允许使用全血、高剪切力、使用整体刺激而非单一激动剂、评估活化血小板产生的凝血酶以及评估纤溶潜力,以使这些测试更符合生理情况。也许需要在更复杂的预测模型中将PFTs的结果与其他预后因素结合起来考虑。本手稿概述了现有PFTs在当代临床实践中的作用和价值,特别关注高危患者可能的个体化抗血小板治疗方案。