Review Question - QID 101368

Warfarin interferes with the synthesis and gamma-carboxylation of glutamic acid in the vitamin K-dependent factors II, VII, IX, and X and proteins C and S.

Warfarin is an anticoagulant that is frequently used in the long-term prevention of venous thrombosis and subsequent pulmonary emboli. Warfarin’s primary effect is to block the extrinsic clotting pathway. Warfarin therapy is monitored through periodic PT/INR measurements. Other clinical uses include prevention of thrombosis in atrial fibrillation and in patients with prosthetic heart valves.

Ramzi and Leeper review the use of anticoagulants in venous thrombosis and pulmonary embolism. Venous thrombosis is treated with initial infusion of unfractionated heparin (or subcutaneous low molecular weight heparin) overlapped with and followed by oral administration of warfarin. The intensity and duration of warfarin therapy is based on individual patient risk factors, but but most patients are treated for at least 3 months.

Berkner reviews vitamin K-dependent carboxylation. Vitamin K epoxidation is used to convert glutamic acid to carboxylated glutamic acid, which activates vitamin K dependent clotting factors. Vitamin K oxidoreductase, the enzymatic target of warfarin, generates the reduced vitamin K cofactor used by the carboxylase.

Illustration A diagrams the mechanism of action of warfarin within the Vitamin K cycle. Illustration B shows the gamma-carboxylation of glutamic acid.

Incorrect answers:
Answer 1: Streptokinase is a thrombolytic that activates plasminogen.
Answer 2: Heparin acts as a cofactor for antithrombin III. Heparin decreases the activity of thrombin and factor Xa.
Answer 3: Rivaroxaban is an oral anticoagulant that is a direct factor Xa inhibitor. It is approved for prophylaxis of venous thrombosis following hip and knee surgery and for prophylaxis of stroke in patients with atrial fibrillation.
Answer 4: Bivalirudin is a reversible direct thrombin inhibitor.