Vitamin K Antagonists (Warfarin)

Warfarin is a vitamin K antagonist that inhibits vitamin K epoxide reductase. Vitamin K epoxide reductase is used to "recycle" vitamin K epoxide to vitamin K, which is the active cofactor in activation of factors II, VII, IX, and X.  Warfarin is used for treatment and prophylaxis of DVT/PE and for stroke prevention in atrial fibrillation as well as other clotting disorders.  Warfarin is metabolized by CYP450, so many drug-drug interactions exist.  Warfarin also causes a hypercoagulative state upon initiation of therapy and can cause skin necrosis. Bleeding is obviously a side effect. Reversal is accomplished by concentrated factor replacement, FFP, and administration of vitamin K.  

Class Drugs

• Warfarin

Class Mechanism of Action

• Inhibits vitamin K epoxide reductase

Vitamin K is a cofactor in the activation of factors II, VII, IX, and X and becomes oxidized to vitamin K epoxide during the activation of factors II, VII, IX, and X

• Vitamin K epoxide reductase, reduces vitamin K epoxide to vitamin K, so the vitamin K can be utilized again

• By inhibiting vitamin K epoxide reductase, coumadin limits the supply of vitamin K, resulting in decreased production of the clotting factors II, VII, IX, and X

Class Applications

• Stroke prophylaxis in atrial fibrillation, protein C and S deficiency, prosthetic heart valves, and antiphospholipid syndrome

• Treatment of DVT/PE

• Prophylaxis of DVT/PE

Class Adverse Effects

Metabolized by CYP450 system leading to many drug-drug interactions

Bleeding

• Level of coagulation is monitored with the INR ratio

• Reversal agents include

Vitamin K

• Fresh frozen plasma

• Concentrated factor replacement

Purple toe syndrome

• Cholesterol emboli from plaques found in blood vessels of toes, painful condition

Skin necrosis and skin lesions

Hypercoagulative state with initiation of therapy

• Early in therapy, reduction of levels of protein C and S (anti-coagulant factors) occur prior to reduction of levels of factors II, VII, IX, and X, resulting in theoretically increased risk of coagulation

• Therapy is generally bridged with another anticoagulant such as enoxaparin

Teratogenic - do not use during pregnancy (heparin and LMWH are preferred in pregnancy)

Drug Table

Drug Name	Application	Comments	Image
Warfarin			"War" "Bus Fare"