Warfarin

Description

Congener of dicumarol. Discovered in spoiled sweet clover hay. (Link KP. Circulation 1959;19:97-101)

Indications

Prevention of thromolism, thromboembolism.

Mechanism

Vitamin K epoxide reductase antagonist. Prevents synthesis of Vit-K dependent clotting factors
II t½=60h
VII 5h
IX 24h
X 48–72h
also protein C, and 8h
protein S 30h
At therapeutic doses, synthesis is reduce 30–50%. May be early pro-thrombotic effect because of the short half life of protein C.

Method of administration

First 2 days: 10mg od. Maintainence dose 3–9 mg titrated by INR.

Pharmacokinetics

Half-life 36–42h.

Monitoring

INR daily at first; 12 weekly when stable. Thromboplastin + Ca++ added to citrated blood. Thromboplastin = tissue extract containing tissue factor and phospholipid necessary to promote the activation of factor X by factor VII INR 1982. ISI (International Sensitivity Index) WHO reference thromboplastin.

Adverse effects

Bleeding, warfarin skin necrosis, 'purple toes'.

Reversal

Stop warfarin. Review indications. Urgent INR. Prothrombin factor concentrate (FFP if not available). Phytomenadione (Vit K) 5 mg IV (cannot then be re-warfarinised for 1/52).

Overdose

Consider cholestyramine po (binds digoxin).

Contraindications

Pregnancy (teratogenic. Use heparin)