Polymorphism induced sensitivity to warfarin: A review of the literature

Abstract

Warfarin is a widely prescribed anticoagulant used for prophylaxis and treatment of venous and arterial thrombosis. Although warfarin is considered very efficacious, it has substantial risks associated with its use, specifically the risk of hemorrhage. Genetic variants associated with the metabolism of (S)-warfarin by cytochrome P450 2C9 may have specific implications on untoward effects. Twelve CYP2C9 allelic variants have been identified, of which CYP2C9*3 and CYP2C9*2 are the most clinically important. Studies have demonstrated that initial dosing of warfarin with CYP2C9*3 with a five-milligram dose caused an increase in the international normalized ratio and significant risk of bleeding. Studies conducted with CYP2C9*2, on the other hand are conflicting. Some data suggest that the CYP2C9*2 variant is associated with an increased propensity for bleeding whereas other studies do not demonstrate a substantial risk of adverse events. Researchers suggest that detection of genetic variants in susceptible individuals will not only decrease the risks associated with warfarin therapy but also decrease costs of adverse events.