Effect of two doses of aspirin on thromboxane biosynthesis andplatelet function in patients undergoing coronary surgery

Journal:Thrombosis and Haemostasis
ISSN:0340-6245
DOI:http://dx.doi.org/10.1160/TH09-07-0470
Issue:2010: 103/3 (Mar) pp. 481–681
Pages:516-524

Effect of two doses of aspirin on thromboxane biosynthesis andplatelet function in patients undergoing coronary surgery

M. Brambilla (1), A. Parolari (1, 2), M. Camera (1, 3), S. Colli (3), S. Eligini (3), C. Centenaro (1), A. Anselmo (1, 4), F. Alamanni (1, 2), E. Tremoli (1, 3)

(1) Centro Cardiologico Monzino, IRCCS, Milano, Italy; (2) Department of Cardiovascular Sciences, Università degli Studi di Milano, Milano, Italy; (3) Department of Pharmacological Sciences, Università degli Studi di Milano, Milano, Italy; (4) Department of Inflammation and Immunology, Istituto Clinico Humanitas, Rozzano, Milano, Italy

Summary

Early post-operative aspirin improves survival in patients undergoing coronary artery bypass graft (CABG). However, most patients do not benefit of aspirin after CABG, still remaining at risk of thrombotic events due to insufficient platelet inhibition, specifically via the thromboxane (TX) pathway. We evaluated the effect of two aspirin doses (100 or 325 mg daily, enteric coated formulations) on platelet function and TX biosynthesis in patients after CABG and assessed whether the incidence of residual platelet reactivity could be reduced by the higher dose. Fifty-six patients undergoing CABG were randomly assigned to 100 or 325 mg aspirin daily for five days in a prospective single-centre study. Treatment effect was assessed by measuring either platelet function (light-transmission aggregometry and point-of-care PFA-100®) or TX biosynthesis in collagen-stimulated platelets, serum, urine, and in lipopolysaccharide (LPS)-cultured whole blood (WB). An insufficient TX inhibition was observed with 100 mg aspirin but not with the higher dose. The different effect of the two doses was, however, highlighted by either TX (platelet- or serum-derived) or by PFA-100® but not by the other assays. In conclusion, early after CABG, the incidence of residual platelet activity was lower in patients who received 325 mg aspirin. Moreover, evidence was provided that different methods yield different results in the detection of aspirin resistance, rendering them not interchangeable.

Keywords

Aspirin, platelet pharmacology, thromboxane, platelet aggregation, coronary surgery

DOI

http://dx.doi.org/10.1160/TH09-07-0470

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