Warfarin and vitamin K.

Warfarin and other 4-hydroxycoumarins are effective antithrombotic agents. They affect four blood coagulation proteins that act sequentially to produce thrombin. Coumarin therapy decreases the biological activity of these proteins, and therefore decreases the rate at which blood clots. As the mechanism by which these drugs act has become clear, it has also been found that vitamin K will overcome the effects of coumarin anticoagulation and can be used to control bleeding side effects of coumarin therapy. Vitamin K is necessary for activity of a liver enzyme, the vitamin K-dependent carboxylase. A second enzyme that recycles an inactive to an active form of the vitamin is inhibited by coumarins. The ability of other liver enzymes to bypass the coumarin-sensitive step greatly enhances the safety of 4-hydroxycoumarins.