Warfarin

Warfarin stands as a cornerstone in anticoagulant therapy, with roots tracing back to its discovery at the Wisconsin Alumni Research Foundation during WWII. Its profound anticoagulant properties soon paved its path into medical therapeutics as a potent antithrombotic agent. The drug exerts its action by targeting the vitamin K epoxide reductase enzyme, crucial in converting vitamin K into its active form. This inhibits the gamma carboxylation of vitamin K dependent clotting factors II, VII, IX, and X, effectively inhibitng the coagulation cascade. Warfarin is distinguished from other anticoagulants in its delayed onset of action. Rather than directly neutralizing existing coagulation factors, it interferes with the synthesis of clotting factors. Vitamin K serves as a pivotal cofactor the synthesis of vitamin K dependent clotting factors, enabling the gamma carboxylation of these clotting factors, as well as protein C and protein S. As a vitamin K antagonist, warfarin inhibits the conversion of vitamin K to its active state. This mechanism underscores the delayed anticoagulant effect, as the culmination of its action awaits the clearance of all active coagulation factors. Warfarin therapy is monitored using prothrombin time (PT) and international normalized ratio (INR). Furthermore, the inhibition of the the anticoagulant factors proteins C and protein S can result in a hypercoaguable state in early warfarin therapy and cause warfarin induced skin necrosis (WISN), which is prevented using a heparin bridge.