Nh. Wallen et M. Ladjevardi, INFLUENCE OF LOW-DOSE AND HIGH-DOSE ASPIRIN TREATMENT ON THROMBIN GENERATION IN WHOLE-BLOOD, Thrombosis research, 92(4), 1998, pp. 189-194
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.