Objectives

The inhibitory effects of P2Y12 receptor antagonist on PAR1- and PAR4-activating peptide (AP)-induced platelet aggregation have not been fully elucidated. The present study aimed to investigate the inhibitory effects of P2Y12 receptor antagonist on PAR1- and PAR4-AP-induced platelet aggregation using platelet-rich plasma (PRP) from individuals including patients with stroke or transient ischemic attack (TIA).

Materials and Methods

PRP was given to 10 healthy individuals pretreated in vitro with cangrelor, then stimulated with adenosine diphosphate (ADP), PAR4-AP, or PAR1-AP. Moreover, 20 patients were enrolled from 148 consecutive patients with acute ischemic stroke or TIA admitted to our institute between December 2017 and April 2019. PRP obtained from each patient before and >7 days after initiation of clopidogrel was similarly stimulated with these agonists. Platelet aggregation was measured using an automatic coagulation analyzer in all participants.

Results

In healthy individuals, ADP- and PAR4-AP-induced platelet aggregations were significantly inhibited depending on the cangrelor concentration in vitro, while PAR1-AP-induced platelet aggregation was slightly inhibited. In patients with stroke or TIA, clopidogrel inhibited ADP-induced platelet aggregation at all concentrations, and significantly inhibited PAR4-AP-induced platelet aggregation at 50 µmol/L of PAR4-AP (p<0.05), especially in 5 patients who showed high reactivity to PAR4-AP. PAR1-AP-induced platelet aggregation was also slightly inhibited.

Conclusions

We showed significant inhibitory effects on PAR4-AP-induced platelet aggregation by clopidogrel in patients with stroke or TIA who had high reactivity to PAR4-AP.

中文翻译：

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P2Y12受体拮抗剂对中风或TIA患者PAR1-和PAR4-AP诱导的血小板聚集的抑制作用

目标

尚未完全阐明P2Y12受体拮抗剂对PAR1和PAR4激活肽（AP）诱导的血小板聚集的抑制作用。本研究旨在研究P2Y12受体拮抗剂对包括中风或短暂性脑缺血发作（TIA）患者的富含血小板的血浆（PRP）对PAR1-和PAR4-AP诱导的血小板聚集的抑制作用。

材料和方法

将PRP给予10名在体外用坎格雷洛预处理的健康个体，然后用二磷酸腺苷（ADP），PAR4-AP或PAR1-AP刺激。此外，在2017年12月至2019年4月期间入院的148例急性缺血性卒中或TIA连续患者中，有20例入选。这些激动剂对氯吡格雷开始前和治疗后7天以上从每名患者获得的PRP进行了类似的刺激。使用自动凝血分析仪测量所有参与者的血小板凝集。

结果

在健康个体中，取决于坎格雷洛尔的体外浓度，ADP和PAR4-AP诱导的血小板聚集受到显着抑制，而PAR1-AP诱导的血小板聚集受到轻微抑制。在卒中或TIA患者中，氯吡格雷在所有浓度下均能抑制ADP诱导的血小板凝集，并在PAR4-AP 50μmol/ L时显着抑制PAR4-AP诱导的血小板凝集（p <0.05），特别是在5例表现出高水平的患者中对PAR4-AP有反应性。PAR1-AP诱导的血小板凝集也受到轻微抑制。

结论

我们显示氯吡格雷对对PAR4-AP有高反应性的中风或TIA患者对PAR4-AP诱导的血小板聚集具有显着的抑制作用。