Wadowski Patricia P, Pultar Joseph, Weikert Constantin, Eichelberger Beate, Panzer Benjamin, Huber Kurt, Lang Irene M, Koppensteiner Renate, Panzer Simon, Gremmel Thomas
Department of Internal Medicine II Medical University of Vienna Vienna Austria.
Department of Blood Group Serology and Transfusion Medicine Medical University of Vienna Vienna Austria.
Res Pract Thromb Haemost. 2019 May 22;3(3):383-390. doi: 10.1002/rth2.12213. eCollection 2019 Jul.
Despite the increasing use of potent P2Y inhibitors, further atherothrombotic events still impair the prognosis of many acute coronary syndrome (ACS) patients. This may in part be attributable to intact platelet aggregation via the human thrombin receptors protease-activated receptor (PAR)-1 and PAR-4.
We studied PAR mediated platelet aggregation in ACS patients following percutaneous coronary intervention (PCI) with stent implantation in a cross-sectional study.
Platelet aggregation to ADP as well as to the PAR-1 agonist SFLLRN and the PAR-4 agonist AYPGKF was assessed by multiple electrode aggregometry in 194 ACS patients on dual antiplatelet therapy with aspirin and either prasugrel (n = 114) or ticagrelor (n = 80) 3 days after PCI.
Based on the consensus cutoff value, high on-treatment residual platelet reactivity to ADP (HRPR ADP) was observed in only 2 prasugrel-treated patients. Both patients with HRPR ADP had also a normal response to SFLLRN and AYPGKF. Among the 112 prasugrel-treated patients with adequate P2Y inhibition, 50 patients (45%) still had a normal response to SFLLRN, and 70 patients (63%) still had a normal response to AYPGKF. Among the 80 ticagrelor-treated patients with adequate P2Y inhibition, 25 patients (31%) still had a normal response to SFLLRN, and 50 (63%) still had a normal response to AYPGKF.
Normal platelet aggregation via PAR-1 and PAR-4 is preserved in many patients with adequate P2Y inhibition by prasugrel and ticagrelor. The present findings may at least in part explain adverse ischemic events despite potent P2Y inhibition.
尽管强效P2Y抑制剂的使用日益增加，但进一步的动脉粥样硬化血栓形成事件仍会损害许多急性冠状动脉综合征（ACS）患者的预后。这可能部分归因于通过人凝血酶受体蛋白酶激活受体（PAR）-1和PAR-4实现的完整血小板聚集。
在一项横断面研究中，我们研究了接受经皮冠状动脉介入治疗（PCI）并植入支架的ACS患者中PAR介导的血小板聚集情况。
通过多电极聚集测定法，对194例接受阿司匹林与普拉格雷（n = 114）或替格瑞洛（n = 80）双联抗血小板治疗的ACS患者在PCI术后3天的血小板对ADP以及PAR-1激动剂SFLLRN和PAR-4激动剂AYPGKF的聚集情况进行了评估。
根据共识临界值，仅在2例接受普拉格雷治疗的患者中观察到对ADP的高治疗期残余血小板反应性（HRPR ADP）。这2例HRPR ADP患者对SFLLRN和AYPGKF也有正常反应。在112例接受普拉格雷治疗且P2Y抑制充分的患者中，50例（45%）对SFLLRN仍有正常反应，70例（63%）对AYPGKF仍有正常反应。在80例接受替格瑞洛治疗且P2Y抑制充分的患者中，25例（31%）对SFLLRN仍有正常反应，50例（63%）对AYPGKF仍有正常反应。
在许多接受普拉格雷和替格瑞洛充分P2Y抑制的患者中，通过PAR-1和PAR-4的正常血小板聚集得以保留。目前的研究结果可能至少部分解释了尽管P2Y抑制强效但仍发生不良缺血事件的原因。
