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Jacqueline Cornelissen, Stephen Kirtland, Eric Lim, Martin Goddard, Sarah Bellm, Kate Sheridan, Stephen Large, Alain Vuylsteke

Biological efficacy of low against medium dose aspirin regimen after coronary surgery: Analysis of platelet function

Keywords: CABG surgery, Aspirin, platelets, thromboxane A2

The failure of aspirin to inhibit platelet function has been documented in patients undergoing coronary artery bypass graft (CABG) surgery, but the causes of aspirin-resistance remain uncertain. The aim of this study was to investigate the efficacy of aspirin in patients undergoing CABG surgery receiving either 100 mg or 325 mg of oral aspirin for 5-days. Platelet function was tested the day before surgery and on day +1 and day +5, and evaluated by changes in collagen-induced thromboxane-A2 (TxA2) release and platelet aggregation following stimulation with collagen, ADP and epinephrine. In all patients, baseline platelet aggregation was significantly inhibited by pre-incubation with in vitro aspirin (150 mol/l), with a mean reduction in TxA2-release of 95.5% (82.3,99.1). After 5-days of oral aspirin, platelet aggregation was significantly inhibited, and was not further inhibited by in vitro aspirin. Oral aspirin was also associated with a 99.5% (97.8, 99.7) reduction in TxA2-release, and with the reversal of the second-phase of ADP-induced aggregation which is TxA2-dependent. In addition a single-dose of 325 mg aspirin on the first post-operative morning may have a greater inhibitory effect on collagen-induced aggregation than 100 mg aspirin. Western blot analysis provided no evidence for the presence of COX-2 in platelets, while the up-regulation of p38-MAPK following platelet-stimulation and surgery was seen. The inhibition of COX-2 (NS398) or p38-MAPK (SB203580) activity did not affect platelet aggregation and TxA2-release on day +5. In summary, there was no evidence for inherent or acquired aspirin-resistance in this surgical population, or for the involvement of either COX-2 or p38-MAPK.

Thrombosis and Haemostasis, Schattauer

Print ISSN: 0340-6245
Volume: 95, 03/2006
Pages: 476 - 482

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