Inhibitory Effects of P2Y12 Receptor Antagonist on PAR1- and PAR4-AP-Induced Platelet Aggregation in Patients with Stroke or TIA |
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| Authors: | Asami Kamada Mie Shimizu Kazumasa Oura Makiko Yoshida Keisuke Tsuda Kiyotaka Oi Yoko Ishigaku Tatsunori Natori Shinsuke Narumi Ryo Itabashi Tetsuya Maeda Yasuo Terayama |
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| Affiliation: | 2. Department of Neurology, Shonan Keiiku Hospital, Japan;2. Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China;3. Department of Neurology, Minda Hospital of Hubei Minzu University, Enshi, Hubei, China;4. Department of Neurology, General Hospital of the Yangtze River Shipping, Wuhan, Hubei, China;5. Department of Neurology, Hanyang Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei, China;2. Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, China;2. Department of Neurology, Shanxi Provincial People''s Hospital, Taiyuan 030012, China;2. Safety Promotions and Injury Prevention Research Centre, Shahid Beheshti University of Medical Sciences, Tehran, I.R., Iran;2. Department of Emergency, Shanghai Fifth People''s Hospital, Fudan University, Shanghai, China;3. Department of Neurology, Shanghai Traditional Chinese and Western Medicine Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China;4. Department of Neurology, Shanghai Ninth People''s Hospital(North Part), Shanghai Jiaotong University, Shanghai, China;2. Department of Neurology, Hopital Maison Blanche, Reims University Hospital, 45 rue Cognacq Jay, 51092 Reims Cedex, France;3. Department of Anesthesiology and Critical Care, Hopital Maison Blanche, Reims University Hospital, 45 rue Cognacq Jay, 51092 Reims Cedex, France;4. University of Medicine of Reims Champagne-Ardennes, 51 rue Cognacq Jay, 51092 Reims Cedex, France;5. Department of emergency medicine, Hopital Maison Blanche, Reims University Hospital, 45 rue Cognacq Jay, 51092 Reims Cedex, France |
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| Abstract: | ObjectivesThe 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 MethodsPRP 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.ResultsIn 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.ConclusionsWe 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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