Objectives: The primary objective was to determine the association of VKORC1 and CYP2C9 polymorphisms, clinical factors and stable warfarin dose in children and adolescents. The secondary objective was to find the bleeding and thrombotic complications of warfarin usage in children and adolescents.
Methods: Children and adolescents who were on long-term warfarin therapy and followed up at the Chiang Mai University Hospital were enrolled. Demographic data including age, gender, anthropometric data, underlying diseases and concurrent medications were collected. The results of international normalized ratio (INR) at stable maintenance warfarin dose were recorded. The blood samples were tested for VKORC1 and CYP2C9 polymorphisms.
Results: We enrolled 57 patients. The median age (interquartile range) was 5.3 years (4.0-8.1 years) and 66.7% were male. The indications for using long-term warfarin were structural heart disease (78.9%) followed by Kawasaki disease with coronary aneurysms (7%). The percentages of VKORC1 polymorphisms were AA 61.4%, GA 33.3% and GG 5.3%, respectively while those of CYP2C9 polymorphisms were *1/*1 94.7%, *1/*3 3.5% and *1/*2 1.8%, respectively. The median dose of warfarin in the patients who had GG genotype of VKORC1 was 0.18 mg/kg/day while those with GA and AA genotype were 0.09 and 0.06 mg/kg/day, respectively (P < 0.001). The median dose of warfarin in the patients who had *1/*1 genotype of CYP2C9 was 0.08 mg/kg/day while that in patients with *2 or *3 alleles was 0.05 mg/kg/day (P = 0.32). In addition, age and body surface area were significant relationship with stable warfarin dose (r = 0.28, P = 0.03) (r = 0.30, P = 0.02), respectively. Bleeding events were found in 10 patients but no thrombotic complication was observed.
Conclusions: The study showed a significant relationship of the VKORC1 polymorphisms with stable warfarin dose in children and adolescents. Therefore, testing for VKORC1 variant may be helpful for adjusting patient’s warfarin dosage to an effective and safe level.
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