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Genetic Variation in Warfarin Metabolism
Ann K. Wittkowsky, Pharm.D., CACP
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
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Wednesday, March 22, 2017