Anticoagulation: a surgical perspective.

Heparin combines with antithrombin III, and the resulting complex inactivates several clotting factors (all are serine proteases) in the coagulation cascade, but the most important steps are inhibition of the conversion of factor X to Xa and the antithrombin effect. Heparin pharmacokinetics are poorly understood, but when the usual doses are given intravenously, heparin is rapidly removed from the blood and has a half-life of approximately 90 minutes. Warfarin is not a true anticoagulant but is readily absorbed after oral administration. It interrupts the coagulation mechanism by interfering with the vitamin K-dependent synthesis of prothrombin and factors VII, IX, and X. This process takes 4 to 5 days. The drug has a long half-life, and its activity is enhanced or blunted by many chemicals. The effective treatment of thromboembolism with heparin, followed by warfarin, requires a basic understanding of the complex pharmacologic aspects and drug interactions.