Role of platelet α2-adrenoreceptor in biological low response to Clopidogrel for patients with non cardioembolic ischemic stroke or transient ischemic attack

American Journal of Translational Research

Guorong Li¹  Claire Boutet²  Fabrice Malergue³  rine Accassat⁴  Magali Epinat⁵  S⁶  Aurélie Montmartin⁷  Céline Chapelle⁸  Arnauld Garcin⁹  Jérôme Varvat^1,10 

[1] Beckman Coulter RD-Research, 13009 Marseille, France;Clinical Research, Innovation and Pharmacology Unit, Saint-Etienne University Hospital Center, North Hospital, Saint-Etienne F-42055, France;Immunology Department, Saint-Etienne University Hospital Center, North Hospital, Saint-Etienne F-42055, France;Inserm, CIC1408, Saint-Etienne F-42055, France;Neurovascular Unit, Saint-Etienne University Hospital Center, North Hospital, Saint-Etienne F-42055, France;Radiology Department, Saint-Etienne University Hospital Center, North Hospital, Saint-Etienne F-42055, France;University of Lyon, UJM-Saint-Etienne, Inserm, Sainbiose U1089, Saint-Etienne F-42023, France;University of Lyon, UJM-Saint-Etienne, PRISMe, CMES, Saint-Etienne F-42023, France;Urology Department, Saint-Etienne University Hospital Center, North Hospital, Saint-Etienne F-42055, France;Vascular and Therapeutic Medicine Department, Saint-Etienne University Hospital Center, North Hospital, Saint-Etienne F-42055, France

关键词: Clopidogrel;    light transmission aggregometry;    flow cytometry;    P-selectin;    α;    2 adrenoreceptors;    stroke;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

Background and purpose: Low biological response to Clopidogrel prescribed after non cardioembolic ischemic stroke or transient ischemic attack (TIA) is a major clinical problem and could explain the recurrence of vascular events. Platelet α2-adrenoreceptors are involved in the high residual platelet reactivity in stable coronary artery disease patients on dual antiplatelet therapy. In the present study we investigated the impact of platelet α2-adrenoreceptors on ADP-induced platelet aggregation and on ADP-induced platelet membrane CD62P (P-selectin) expression, a marker of platelet activation on blood samples from patients hospitalized at the acute phase of a non cardioembolic ischemic stroke or TIA. Methods: 72 consecutive patients were prospectively recruited over the course of two years in a monocentric study. Patients received a daily 75 mg-dose of Clopidogrel. ADP-induced platelet aggregation was measured alone, with low dose epinephrine or with atipamezole, a selective α blocker of α2-adrenoreceptors, by Light Transmittance Aggregometry (LTA). Platelet membrane expression of P-selectin was measured by flow cytometry with either ADP alone or combined with epinephrine. Results: Epinephrine at low dose stimulated ADP-induced platelet membrane expression of CD62P whereas Atipamezole significantly inhibited 10 µM ADP-induced platelet aggregation. Conclusions: Our study showed the role of platelet α2-adrenoreceptors in biological low response to Clopidogrel for patients hospitalized for a non-cardioembolic ischemic stroke or TIA. Atipamezole could improve the status of biological response to Clopidogrel.

【 授权许可】

CC BY-NC