Inhibitory Effects of P2Y12 Receptor Antagonist on PAR1- and PAR4-AP-Induced Platelet Aggregation in Patients with Stroke or TIA

P2Y12 氯吡格雷 血小板 坎格雷洛 敌手 药理学 二磷酸腺苷 医学 富血小板血浆 腺苷 抑制性突触后电位 冲程(发动机) 血小板活化 化学 阿司匹林 受体 内科学 血小板聚集 机械工程 工程类
作者
Asami Kamada,Mie Shimizu,Kazumasa Oura,Makiko Yoshida,Keisuke Tsuda,Kiyotaka Oi,Yoko Ishigaku,Tatsunori Natori,Shinsuke Narumi,Ryo Itabashi,Tetsuya Maeda,Yasuo Terayama
出处
期刊:Journal of stroke and cerebrovascular diseases [Elsevier]
卷期号:30 (3): 105547-105547
标识
DOI:10.1016/j.jstrokecerebrovasdis.2020.105547
摘要

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.
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