Enzyme polymorphism in warfarin dose management after pediatric cardiac surgery

BACKGROUND: Warfarin is an anticoagulant and is widely used for the prevention of thromboembolic events. Genetic variants of the enzymes that metabolize warfarin, i.e. cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1), contribute to differences in patients' responses to various warfarin doses. There is, however, a dearth of data on the role of these variants during initial anticoagulation in pediatric patients. OBJECTIVES: We aimed to evaluate the role of genetic variants of warfarin metabolizing enzymes in anticoagulation in a pediatric population. PATIENTS AND METHODS: In this prospective cohort study, 200 pediatric patients, who required warfarin therapy after cardiac surgery, were enrolled and divided into two groups. For 50 cases, warfarin was prescribed based on their genotyping (group 1) and for the remaining 150 cases, warfarin was prescribed based on our institute routine warfarin dosing (group 2). The study endpoints were comprised of time to reach the first therapeutic international normalization ratio (INR), time to reach a stable warfarin maintenance dose, time with over-anticoagulation, bleeding episodes, hospital stay days and stable warfarin maintenance dose. RESULTS: There was no significant difference concerning the demographic data between the two groups. The time to stable warfarin maintenance dose and hospital stay days were significantly lower in group 1 (P <0.001). However, there was no statistically significant difference in time to reach the first therapeutic INR, time with over-anticoagulation and bleeding episodes, between the two groups. CONCLUSIONS: The determination of warfarin dose, based on genotyping, might reduce the time to achieve stable anticoagulation of warfarin dose and length of hospital stay.