Influence of low- 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. Thrombin generation in whole blood was monitored by repeated measurements of prothrombin fragment 1+2 (F1+2) in plasma prepared from untreated whole blood left to clot at 37 degrees C. Experiments with a platelet inhibiting agent (iloprost, a prostacyclinanalogue) and platelet-activating compounds (collagen and a thromboxane analogue), indicated that the formation of thrombin in this system is partly dependent on platelet function. High dose aspirin (500 mg daily) attenuated thrombin generation, whereas low-dose treatment (75 mg daily) failed to attenuate thrombin formation significantly. Collagen-induced platelet aggregation in whole blood, used to monitor antiplatelet effects of aspirin, showed profound inhibition of platelet aggregation already at 75 mg of aspirin; 500 mg did not inhibit platelet aggregation further. Our results show that aspirin suppresses thrombin formation in whole blood in a dose-dependent fashion and that the "antithrombin" effects of aspirin require higher doses than the antiaggregating effects. The mechanism(s) behind the "antithrombin" effects of aspirin is at present unclear but may involve thromboxane-independent mechanisms, such as acetylation of platelet membrane receptors or coagulation factors.