期刊
THROMBOSIS AND HAEMOSTASIS
卷 110, 期 4, 页码 777-784出版社
SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN
DOI: 10.1160/TH13-05-0400
关键词
Aspirin; platelet function; purinergic pathway
资金
- Ministry of Education (Spain)
- Spanish Society of Cardiology (Beca de la Seccion de Cardiopatia Isquemica para Formacion e Investigacion Post Residencia en el Extranjero - Sociedad Espanola de Cardiologia)
Different aspirin dosing regimens have been suggested to impact outcomes when used in combination with adenosine diphosphate (ADP) P2Y(12) receptor antagonists. Prior investigations have shown that not only aspirin, but also potent ADP P2Y(12) receptor blockade can inhibit thromboxane A2-mediated platelet activation. The impact of aspirin dosing on ADP mediated platelet activities is unknown and represents the aim of this in vitro pilot pharmacodynamic (PD) investigation. Twenty-six patients with stable coronary artery disease on aspirin 81 mg/day and P2Y(12) naive were enrolled. PD assessments were performed at baseline, while patients were on 81 mg/day aspirin and after switching to 325 mg/day for 7 +/- 2 days with and without escalating concentrations (vehicle, 1, 3, and 10 mu M) of prasugrel's active metabolite (P-AM). PD assays included flow cytometric assessment of VASP to define the platelet reactivity index (PRI) and the Multiplate Analyzer (MEA) using multiple agonists [ADP, ADP + prostaglandin (PGE1), arachidonic acid (AA), and collagen]. Escalating P-AM concentrations showed incremental platelet P2Y(12) inhibition measured by VASP-PRI (p<0.001). However, there were no differences according to aspirin dosing regimen at any P-AM concentration (vehicle: p=0.899; 1 mu M: p=0.888; 3 mu M: p=0.524; 10 mu M: R=0.548). Similar findings were observed in purinergic markers assessed by MEA (ADP and ADP+PGE1)., P-AM addition significantly reduced AA and collagen induced platelet aggregation (p<0.001 for all measures), irrespective of aspirin dose. In, conclusion, aspirin dosing does not appear to affect PD measures of ADP-mediated platelet reactivity irrespective of the degree of P2Y(12) receptor blockade. P2Y(12) receptor blockade modulates platelet reactivity mediated by alternative activators.
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