Jérôme Varvat1,2, Magali Epinat1,2, Aurélie Montmartin2, Sandrine Accassat3,4, Claire Boutet2,5, Arnauld Garcin6, Guorong Li7, Fabrice Malergue8, Céline Chapelle6, Silvy Laporte2,4,6, Pierre Garnier1,2, Claude Lambert9, Nora Mallouk3,10, Patrick Mismetti3,1,2,6. 1. Neurovascular Unit, Saint-Etienne University Hospital Center, North Hospital Saint-Etienne F-42055, France. 2. University of Lyon, UJM-Saint-Etienne, Inserm, Sainbiose U1089 Saint-Etienne F-42023, France. 3. Vascular and Therapeutic Medicine Department, Saint-Etienne University Hospital Center, North Hospital Saint-Etienne F-42055, France. 4. Inserm, CIC1408 Saint-Etienne F-42055, France. 5. Radiology Department, Saint-Etienne University Hospital Center, North Hospital Saint-Etienne F-42055, France. 6. Clinical Research, Innovation and Pharmacology Unit, Saint-Etienne University Hospital Center, North Hospital Saint-Etienne F-42055, France. 7. Urology Department, Saint-Etienne University Hospital Center, North Hospital Saint-Etienne F-42055, France. 8. Beckman Coulter R&D-Research 13009 Marseille, France. 9. Immunology Department, Saint-Etienne University Hospital Center, North Hospital Saint-Etienne F-42055, France. 10. University of Lyon, UJM-Saint-Etienne, PRISMe, CMES Saint-Etienne F-42023, France.
Abstract
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.
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 diseasepatients 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.
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