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Genetic Variation in Warfarin Metabolism

Ann K. Wittkowsky, Pharm.D., CACP
September 2004

Review: Joffe HV, Xu R, Johnson FB, Longtine J, Kucher N, Goldhaber SZ. Warfarin dosing and cytochrome P450 2C9 polymorphisms. Thromb Haemost. 2004 Jun;91(6):1123-8.

Variant genetic expression of cytochrome p450 2C9 is associated with significant reductions the metabolism of S-warfarin. Previous studies have confirmed that patients with CYP2C9 polymorphisms have decreased warfarin dosing requirements. Other studies have suggested a higher incidence of bleeding complications in patients with CUP2C9 polymorphisms.

This paper found that after excluding other reasons for low warfarin dosing requirements, 100% of patients who required < 1.5mg/day of warfarin to reach a goal INR of 2-3 had CYP2C9 polymorphisms CYP2C9*2 or CYP2C9*3. Over an average of 26 months of follow-up, these patients were more likely to experience at least 1 asymptomatic INR > 6.0. However, these patients were no more likely to experience bleeding complications than patients with mean warfarin dosing requirements of 4-6mg/day or > 10mg/day, in whom CYP2C9 polymorphisms were less common. The authors suggested that the close warfarin monitoring provided by the Anticoagulation Service that managed warfarin in these patients may have limited the risk of bleeding complications.

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