Clinical study of warfarin individualized anticoagulation based on CYP2C9 and VKORC1 genotypes for acute pulmonary thromboembolism patients

Objective To evaluate the clinical application of warfarin individualized anticoagulation based on CYP2C9 and VKORC1 genotypes in patients with acute pulmonary thromboembolism. Methods Seventy-two patients with acute pulmonary thromboembolism in the General Hospital of Tianjin Medical University from July 2014 to June 2015 were enrolled. The CYP2C9 and VKORC1 genetic polymorphisms were detected by PCR and gene chip technology. The patients were randomly divided into study group (n=34) and control group (n=38). The patients in the study group were given warfarin dose according to the International Warfarin Pharmaeogenetics Consortium (IWPC) at the first 3 days, and the patients in the control group received the dose of 3 mg/d at the first 3 days. Then all the patients adjusted the warfarin dose according to the international normalized ratio (INR) and routine clinical practice. The INR were measured routinely at 1, 4, 6, 8, 14, 21, 28, 42, 56, 84 d, and warfarin dose were recorded everyday. Results The CYP2C9 and VKORC1 genetic polymorphisms in the two groups showed no significant differences (χ2=0.941, P=0.919). Compared with the control group, the first time to INR target range [(8.8 ± 3.6) d vs. (10.7 ± 2.9) d; t=2.481, P=0.016] and time-to-stable dose [(14.3 ± 6.1) d vs. (19.2 ± 6.5) d; t=3.252, P=0.002] were much shorter, number of stable dosage at 2 weeks (19/34 vs. 12/38, χ2=4.323, P=0.038) were much higher in the study group. Meanwhile, the INR in the two groups were changed over time (F=42.016, P<0.001), and the INR at 4, 6, 8, 10, 12, 14, 19, 21, 28 d in the study group also showed statistical significance (all P<0.05). Conclusion The warfarin individualized anticoagulation based on CYP2C9 and VKORC1 genotypes can shorten the adjustment time to reach INR target range and warfarin stable dose, and have a guiding role at the early stage of anticoagulation. Key words: Genes; Pulmonary embolism; Warfarin; Anticoagulation; Individualized medicine