Clinical trials over the last decade have demonstrated that aspirin is an effective antithrombotic agent. Aspirin irreversibly inhibits the enzyme cyclo-oxygenase, which in the platelet is responsible for the production of thromboxane A2, a platelet-aggregating agent; and, in vascular wall cells, cyclooxygenase is responsible for the production of prostacyclin (PGI2), an inhibitor of platelet aggregation. Thus, aspirin has the potential to be both antithrombotic and thrombogenic. Low doses of aspirin (325 mg or less) inhibit cyclo-oxygenase in platelets and vascular wall cells, but the inhibitory effect on platelet thromboxane A2 synthesis is greater and lasts longer than its effect on vascular wall PGI2 synthesis.1
The therapeutic importance of inhibiting PGI2 may have been overestimated in the past. Experimentally, aspirin is only thrombogenic at very high doses2 (200 mg/kg), which far exceed the minimum dose required to inhibit PGI2 production. This suggests that inhibition of PGI2 production may not be the
Hirsh J. The Optimal Antithrombotic Dose of Aspirin. Arch Intern Med. 1985;145(9):1582–1583. doi:10.1001/archinte.1985.00360090046005
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