Clopidogrel affects leukocyte dependent platelet aggregation by P2Y 12 expressing leukocytes

Clopidogrel affects leukocyte dependent platelet aggregation by P2Y 12 expressing leukocytes,10.1007/s00395-009-0073-8,Basic Research in Cardiology,Ph

Clopidogrel affects leukocyte dependent platelet aggregation by P2Y 12 expressing leukocytes   (Citations: 3)
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Up to 30% of all patients who are treated with a coronary stent do not respond sufficiently to antiplatelet therapy. This condition results in an increased risk for thrombotic complications such as stent thrombosis and myocardial infarction. The aim of the study was to determine clinical parameters modulating ASA and clopidogrel responsiveness. Patients were enrolled into three groups: (A) Patients with coronary artery disease without recent PCI treated with 100 mg/day ASA (n = 67). (B) Patients who underwent coronary stent implantation taking 100 mg/day ASA and 75 mg/day clopidogrel (n = 87). (C) Patients in whom CAD was excluded by angiography and who were not treated with anti-platelet medication served as controls (n = 32). Platelet aggregation was determined by impedance aggregometry using the Multiplate® point of care device. Drug response was differentiated by stimulation of whole blood with arachidonic acid (AA, ASA responsiveness) or adenosine diphosphate (ADP, clopidogrel responsiveness). P2Y12 receptor expression was determined by RT-PCR. ADP induced platelet aggregation correlated with the leukocyte count (r = 0.61, p < 0.001) suggesting that platelets and leukocytes interact functionally. Clopidogrel treatment abolished the influence of leukocytes on platelets and caused decreased leukocyte activation. We detected the expression of the clopidogrel target P2Y12 on leukocytes suggesting that clopidogrel may act directly on these cells and not only on platelets. In contrast to ASA responsiveness, clopidogrel response correlated with body mass index (r = 0.34; p = 0.001). In conclusion, (1) leukocytes influence ADP induced platelet aggregation most likely by expression of the P2Y12 receptor. This interaction is abolished by clopidogrel. Therefore, clopidogrel may act directly on leukocytes via the P2Y12 receptor. (2) Clopidogrel may be under dosed in obese patients.
Journal: Basic Research in Cardiology - BASIC RES CARDIOL , vol. 105, no. 3, pp. 379-387, 2010
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    • ...As eNOS-specific and unspecific compounds can activate eNOS and lead to vasodilation or cardioprotection [12, 23, 40] and clopidogrel effects have been described on nonplatelet cells [4, 19], we examined the therapeutic effects of chronic P2Y12 inhibition with clopidogrel on endothelial function in CHF rats after experimental MI...

    Andreas Schäferet al. Clopidogrel improves endothelial function and NO bioavailability by se...

    • ...Patients were analysed in intra-individual time courses but also compared to 67 control patients (control group, CG) who were recruited earlier [5]...
    • ...Platelet aggregation was quantified using a point of care device (Multiplate, Dynabyte GmbH, Munich, Germany) that measures the platelet aggregation dependent change of impedance in whole blood [5]...

    Philipp Diehlet al. Discontinuation of long term clopidogrel therapy induces platelet rebo...

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