Warfarin and Other "Anti"-Vitamin K Anticoagulants: Pharmacodynamics and Clinical Use

Fortuitously discovered after an episode of bovine hemorrhagic disease, the oral antivitamin K anticoagulants inhibit a posttranslational modification of coagulation factors II, VII, IX, and X that is essential for bioactivity. They also influence formation of regulatory proteins C and S. Although their influence on the extrinsic pathway may be measured using the prothrombin time, a modification thereof produces the International Normalized Ratio (INR) which should allow for less interlaboratory variation. Finding utility in both prophylaxis and treatment of thromboembolic disease, these agents have rendered themselves important pharmacologic tools in the management of deep venous thrombosic, nonvalvular atrial fibrillation, structural heart disease, myocardial infarction, and following major surgical procedures.