INFLUENCE OF LOW-DOSE AND HIGH-DOSE ASPIRIN TREATMENT ON THROMBIN GENERATION IN WHOLE-BLOOD

The effects of two doses of aspirin (75 and 500 mg/day during 1 week) on thrombin generation was investigated in healthy volunteers. Thrombi n generation in whole blood was monitored by repeated measurements of prothrombin fragment 1+2 (F1+2) in plasma prepared from untreated whol e blood left to clot at 37 degrees C. Experiments with a platelet inhi biting agent (iloprost, a prostacyclinanalogue) and platelet-activatin g compounds (collagen and a thromboxane analogue), indicated that the formation of thrombin in this system is partly dependent on platelet f unction. High dose aspirin (500 mg daily) attenuated thrombin generati on, whereas low-dose treatment (75 mg daily) failed to attenuate throm bin formation significantly. Collagen-induced platelet aggregation in whole blood, used to monitor antiplatelet effects of aspirin, showed p rofound inhibition of platelet aggregation already at 75 mg of aspirin ; 500 mg did not inhibit platelet aggregation further. Our results sho w that aspirin suppresses thrombin formation in whole blood in a dose- dependent fashion and that the ''antithrombin'' effects of aspirin req uire higher doses than the antiaggregating effects. The mechanism(s) b ehind the ''antithrombin'' effects of aspirin is at present unclear bu t may involve thromboxane-independent mechanisms, such as acetylation of platelet membrane receptors or coagulation factors. (C) 1998 Elsevi er Science Ltd.