基因多态性指导华法林给药临床研究

Gene Polymorphism Guided the Clinical Study of Warfarin Administration

关键词:  基因  静脉血栓  华法林  个体化给药

Key words:  gene  venous thrombus  warfarin  individualized drug administration

摘要:

目的 观察基因多态性指导静脉血栓患者华法林个体化给药方案的临床疗效和安全性。方法 采用前瞻性的队列研究方法，分别建立基因给药组和固定剂量组2个队列。基因给药组病例的华法林初始剂量根据该患者华法林相关基因多态性检测结果，采用IWPC模型制定华法林初始给药方案；固定剂量组初始给药方案为华法林3 mg·d^-1。收集入组病例病理生理指标，并随访3个月。比较2组病例的临床疗效和不良反应的发生情况。结果 基因给药组华法林治疗后达到目标国际标准化比值（international standardization ratio，INR）的时间[（5.65±2.30）d]比固定剂量组[（8.51±3.97）d]快（P<0.001）。使用华法林2周及4周后基因给药组时间百分比（time in therapeutic range，TTR）分别达到73.00%和78.26%，显著高于固定剂量组[TTR百分比值分别为58.11% （P=0.001）和64.67% （P<0.001）]；但4周后TTR在2组之间的差异不具有统计学意义。基因给药组小出血事件发生率比固定剂量组少（P<0.05），但异常INR值（INR≥4.0）以及主要的出血事件差异无统计学意义。结论 基因给药组华法林的临床疗效优于固定剂量组，同时小出血事件发生率较固定剂量组少。

Abstract:

OBJECTIVE To investigate the clinical efficacy and safety of gene polymorphism guiding the individualized administration of warfarin in patients with venous thrombosis. METHODS A prospective cohort study was conducted to establish two cohorts, the genotyped guided group and fixed dose group. The initial warfarin dose of the patients in the genotyped guided group was based on the results of warfarin-related gene polymorphism detection, and IWPC model was used to formulate initial warfarin administration plan. The initial warfarin dose of the fixed dose group was 3 mg·d^-1. Pathophysiological parameters of the enrolled patients were collected and a three-months follow-up was carried out. The clinical efficacy and adverse reactions were compared between the two groups. RESULTS The time to reach the target international standardization ratio(INR) after warfarin treatment in the gene administration group[(5.65±2.30)d] was faster than that in the fixed dose group[(8.51±3.97)d](P<0.001). After 2 weeks and 4 weeks of warfarin use, the time in therapeutic range(TTR) of the gene administration group reached 73.00% and 78.26%, respectively, significantly higher than that of the fixed dose group(TTR 58.11% and 64.67%)(P=0.001, P<0.001). However, the difference of TTR after 4 weeks between the two groups was no statistically significant. The incidence of minor bleeding events in the gene administration group was lower than that in the fixed dose group(P<0.05), but the differences of major bleeding events and the abnormal INR value(INR ≥ 4.0) were not statistically significant. CONCLUSION The clinical efficacy of warfarin in gene administration group is better than that in fixed dose group, and the incidence of small bleeding events was less than that in fixed dose group.