Abstract 483: Reverse Effect of Aspirin: is the Prothrombotic Effect After Aspirin Discontinuation Mediated by COX 2 Blockade ?
An increased risk of Acute Coronary Syndrome (ACS) and Stroke after aspirin discontinuation was reported in recent clinical surveys. To clarify the mechanism of these findings, we assessed the hypothesis that a very small amount of aspirin could remain and act through a different COX2/COX1 sensitivity leading to a prothrombotic effect. An in vivo model of laser-induced thrombosis was used in rat mesenteric circulation, expressed as Number of Emboli (NE) and Duration of Embolisation (DE), as well as Induced Hemorrhagic Time (IHT) performed on the tail. Wistar rats (n=72) were randomly divided in 6 groups. SC-560 or NS-398 were respectively used as specific COX 1 or 2 blockers in one dose of 10 mg/kg, 1 ml/kg b.w, suspended in a CMC solution (0.5%). COX blockers were administered intragastrically 90min. before the laser procedure. One ultra-low dose of aspirin (ULDA) (334x10−11 mol/ml) 1 ml/kg b.w, was injected subcutaneously, 60 min before the laser procedure. CMC solution or distilled water were used as placebo (Plac). Results are expressed as mean±SEM (Table 1⇓). Student t test was used for statistical analysis and p<0.05 was considered significant. ULDA was found to increase the NE and the DE, confirming its prothrombotic effect. This effect was not changed by pretreatment with SC-560 and a shorter IHT was also observed. NS-398 inhibited the action of ULDA, suggesting a COX2-mediated pathway of effect. In conclusion: The prothrombotic activity of ULDA could be due to inhibition of COX 2 mediated PGI2 production in the endothelium. This could also explain why increased ACS and Stroke risk are reported after aspirin discontinuation.