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Vol. 36, No. 1, 2007/2008
Issue release date: March 2008
Pathophysiol Haemos Thromb 2007–08;36:40–44

Reverse Effect of Aspirin: Is the Prothrombotic Effect after Aspirin Discontinuation Mediated by Cyclooxygenase 2 Inhibition?

Doutremepuich C. · Aguejouf O. · Eizayaga F.X. · Desplat V.
aLaboratoire d’Hématologie, UFR des Sciences Pharmaceutiques, Université Victor Segalen Bordeaux 2, Bordeaux, France; bCEBBAD, Facultad de Medicina, Universidad Maimónides, Buenos Aires, Argentina

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Background: While aspirin is the drug most often used to prevent cardiovascular complications, its discontinuation induces an increased risk of acute coronary syndrome and ischemic stroke in some patients. Objectives: We hypothesized that infinitesimal concentrations of aspirin could persist in plasma after its discontinuation, thereby inducing a prothrombotic effect that could be due to a modification in the mechanism of action of aspirin via the cyclooxygenase 1 (COX-1) and COX-2 pathways. Methods and Results: We studied the effects of ultra-low-dose aspirin (ULDA) as well as those of sc-560 and ns-398, specific COX-1 and COX-2 inhibitors, on induced hemorrhagic time and in a model of laser-induced thrombosis in rats. In the laser-induced thrombosis model, ULDA treatment increased the number of emboli and the duration of embolization, thereby confirming its prothrombotic effect described in previous publications. This effect was also observed in rats pretreated with sc-560 but not in those pretreated with ns-398. Conclusions: We demonstrated that ULDA induced a prothrombotic effect in the rats studied. This strongly suggests that a very small amount of aspirin could remain in the patient’s blood after aspirin therapy, leading to cardiovascular complications. This effect may be mediated by the COX-2 pathway.

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