| Objective To observe the variation in the INR change, dosage adjustment, and the incidence of adverse events of China Han patients with acute pulmonary thromboembolism under a warfarin individualized anticoagulant medication based on CYP2C9 and VKORC1 genotypes, to evaluate whether the individualized anticoagulant medication could shorten the adjustment time of warfarin and reduce the incidence of adverse events compare to the traditional warfarin anticoagulant medication, and explore the meaning of individualized warfarin anticoagulant medication in China Han patients.Method(1)collecting data: Ninety-eight patients with acute pulmonary thromboembolism(APTE) in the Emergency Medicine Department of the General Hospital of Tianjin Medical University from July 2014 to June 2015 were enrolled, 51 people were male, 47 people were female. Patients’ Gender, age, height, weight, smoking history and other demographic information were recorded, and laboratory data were collected. All the patients’ CYP2C9 and VKORC1 genetic polymorphisms were detected by PCR and genechip technology.(2)research method: The patients were randomly divided into a study group and a control group. For patients assigned to the study group, warfarin doses were prescribed according to website( http://www.warfarindosing.org) built from the IWPC and Gage pharmacogenetic-based algorithms for the first 3 days. Patients in the control group received the dose of 3mg/d for the first 3 days. After the initiation period, the treatment of all patients was managed according to the international normalized ratio(INR) and routine clinical practice. The target INR for APTE patients was 2 to 3.All the patients were followed up for 12 weeks, INR was measured routinely in days1,4,6,8,10,12,14,19,21,28,42,56 and 84, warfarin dose of everyday and incidence of adverse events was recorded.(3)statistical analysis: The non parametric K-S method was used to evaluate the normality of the experimental data. The measurement data of normal distribution was represented by mean ± standard deviation( sx ±), two independent sample T test or paired-samples T tested wsa used to compare the differeces between the two groups of measurement data. The non parametric test of two independent samples was rank sum test.All the statistical analyses were made by two-sided test, P < 0.05 for the difference was statistically significant.Results There was no significant difference in gender, age, height, body weight, body surface area, CYP2C9 and VKORC1 genotype distribution between the study groups and the control group. The time required to reach a therapeutic INR(2~3)in study group was reduced compared with control group( Day: 8.8±3.6 vs. 10.7±2.9, P<0.05); the time required to reach a stable dose in study group was also reduced compared with control group( Day: 14.3±6.1 vs. 19.2±6.5, P<0.05); the percentage of people reaching stable dose within 2 weeks was higher in study group than control group(n/%: 19/55.9 vs. 12/31.6, P<0.05). However, there was no significant difference between the two groups in the incidence of excessive anticoagulation(INR>4 and bleeding events)(n/%:3/8.8 vs. 5/13.2,P>0.05),and the dosing adjustment did not differ significantly between the two groups(mg:0.325 vs. 0,P>0.05). Despite this,the difference in mean INR between the two groups was greatest near the start of the trail.Conclusion The warfarin individualized medication based on CYP2C9 and VKORC1 genotypes can significantly shorten the adjustment time to reach therapeutic INR and warfarin stable dose, and is clinically instructive in the initial stage of anticoagulation. |
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