Abstract 5009: Prothrombotic Effect After Aspirin Discontinuation is Cox 2-dependent
Aspirin (ASA) discontinuation for surgery or non-compliance increases the risk of a thrombotic accident or stent thrombosis, especially after the second week. Previous papers have shown that 8 to 10 days after a single high dose of ASA in the rat, a pro-thrombotic state develops. We hypothesized that insignificant amounts of ASA may remain after discontinuation and cause a prothrombotic COX 2-mediated effect.
Mehtods: Wistar rats (1000) were separated into 100 groups. Induced hemorrhagic time in seconds (IHT) and Laser-induced thrombosis, expressed as number of emboli (NE), were used. ASA was injected in 100 mg/kg, 1 mg/kg or 1/100 dilutions (Dil) 5, 9 or 15, subcutaneously, in a final volume of 1 ml/kg. Sterilized water was used as placebo. Selective inhibitors of COX 1 (SC-560) or COX 2 (NS-398) were used at 2.5, 5, 7.5 and 10 mg/kg, intragastrically. Carboxy-methyl-cellulose, the vehicle of COX inhibitors, was used as control. Each group was compared with its control with the t-test, p<0.05 was considered significant.
Results: (only highest or lowest doses shown) the highest dose of ASA prolonged IHT and decreased thrombosis. A clear opposite trend was observed with the highest dilution, which generated a shortened IHT and an increased NE. SC-560 produced an effect similar to the higher doses of ASA, prolonged IHT and decreased NE, proportional to dose increase. This effect of COX 1 inhibition was antagonized by the highest ASA dilutions. NS-398 created a pro-thrombotic effect that was antagonized by ASA at higher doses. There was no further effect of the highest dilution of ASA after NS-398.
Conclusion: There is a clear prothrombotic effect of ASA Dil 15 that is opposed to COX 1 inhibition and which is inhibited by COX 2 inhibition. COX 2 inhibition and Dil 15 of ASA have similar effects. The prothrombotic effect of the highest dilution of ASA is achieved through COX 2 inhibition and may be blamed for the thrombotic accidents and stent thrombosis described after ASA discontinuation.