Vol 67, No 6 (2009)
Other
Published online: 2009-06-24
Original article
Thrombin formation and platelet activation at the site of vascular injury in patients with coronary artery disease treated with clopidogrel combined with aspirin
DOI: 10.33963/v.kp.80106
Kardiol Pol 2009;67(6):591-598.
Abstract
Background: Data on the effects of oral antiplatelet agents on blood coagulation in vivo are conflicting. The platelet glycoprotein (GP) IIIa PlA2 allele has been suggested to modulate antithrombotic actions of clopidogrel.
Aim: We investigated whether clopidogrel combined with aspirin affects local thrombin formation and platelet activation triggered by vascular injury.
Method: We studied patients with stable coronary artery disease on chronic aspirin therapy randomised to addition of clopidogrel 75 mg/d (n = 30) or continuation of aspirin 100 mg/d (n = 30) for 4 weeks. Markers of thrombin generation [thrombin-antithrombin complexes (TAT) and prothrombin 1.2 fragments (F1.2)] and markers of platelet activation [soluble CD40 ligand (sCD40L) and P-selectin] were determined in the supernatant of blood samples obtained from a microvascular injury site.
Results: Total amounts of thrombin markers produced at the site of injury were similar before and after addition of clopidogrel, whereas platelet release of sCD40L and P-selectin was lower during treatment with aspirin + clopidogrel by 33.8% and 27.8% (p < 0.001), respectively. Patients in the highest tertile of reduction in platelet activation had previous myocardial infarction and peripheral arterial disease and released the highest amounts of sCD40L and P-selectin at baseline. TAT and F1.2 generation as well as sCD40L or P-selectin release were not influenced by the presence of the PlA2 allele.
Conclusion: Our study shows that clopidogrel combined with aspirin does not reduce thrombin formation following vascular injury, but attenuates platelet sCD40L and P-selectin release.
Aim: We investigated whether clopidogrel combined with aspirin affects local thrombin formation and platelet activation triggered by vascular injury.
Method: We studied patients with stable coronary artery disease on chronic aspirin therapy randomised to addition of clopidogrel 75 mg/d (n = 30) or continuation of aspirin 100 mg/d (n = 30) for 4 weeks. Markers of thrombin generation [thrombin-antithrombin complexes (TAT) and prothrombin 1.2 fragments (F1.2)] and markers of platelet activation [soluble CD40 ligand (sCD40L) and P-selectin] were determined in the supernatant of blood samples obtained from a microvascular injury site.
Results: Total amounts of thrombin markers produced at the site of injury were similar before and after addition of clopidogrel, whereas platelet release of sCD40L and P-selectin was lower during treatment with aspirin + clopidogrel by 33.8% and 27.8% (p < 0.001), respectively. Patients in the highest tertile of reduction in platelet activation had previous myocardial infarction and peripheral arterial disease and released the highest amounts of sCD40L and P-selectin at baseline. TAT and F1.2 generation as well as sCD40L or P-selectin release were not influenced by the presence of the PlA2 allele.
Conclusion: Our study shows that clopidogrel combined with aspirin does not reduce thrombin formation following vascular injury, but attenuates platelet sCD40L and P-selectin release.
Keywords: clopidogrelthrombincoronary artery diseaseaspirinvascular injuryplatelets
