目的 探讨重症监护室(ICU)患者中,维生素K环氧化物还原酶复合体亚单位1(VKORC1)和细胞色素氧化酶P450 2C9(CYP2C9)基因多态性检测对华法林抗凝治疗的指导价值。方法 回顾性分析2019-06至2023-06火箭军特色医学中心ICU收治的合并抗凝指征(心房颤动、深静脉血栓、肺栓塞)患者90例。研究组(30例)为进行基因检测并根据检测结果指导华法林用药的患者;对照组(60例)为未进行基因检测执行临床常规华法林用药策略的患者,对两组进行为期6个月的随访。比较两组一般临床资料信息、研究组基因型分布情况、国际标准化比值(INR)达标时间、治疗窗内的时间比例(TTR)、华法林起始及维持剂量、出血事件发生率及INR≥4.0事件发生率。结果 研究组INR达标时间(9.56±1.68) d,短于对照组 的(11.12±2.03) d;研究组TTR为(72.56±6.90)%,高于对照组 的(64.45±7.82)%,差异有统计学意义(P＜0.05)。研究组华法林起始和维持剂量分别为(2.91±0.73)mg/d、(3.17±0.81 )mg/d,与对照组相比差异均无统计学意义。研究组中小出血事件发生6例(20.00%),低于对照组的27例(45.00%),差异有统计学意义(P＜0.05),两组大出血事件发生率差异无统计学意义。研究组INR≥4.0发生率为16.67%,低于对照组的40.00%,差异有统计学意义(P＜0.05)。结论 ICU合并抗凝指征患者进行VKORC1和CYP2C9基因多态性检测指导华法林用药,有利于增强抗凝疗效、减少相关不良反应,进而提高用药安全性。
Abstract
Objective To investigate the guiding value of vitamin K epoxide reductase complex subunit 1 (VKORC1) and cytochrome oxidase P450 2C9 (CYP2C9) gene polymorphism detection on anticoagulation therapy of warfarin in intensive care unit (ICU) patients. Methods Ninety patients with indication of anticoagulation (atrial fibrillation, deep vein thrombosis and pulmonary embolism) admitted to ICU of Characteristics Medical Center of PLA Rocket Force from June 2019 to June 2023 were retrospectively analyzed. The study group (30 cases) underwent genetic testing and were instructed to use warfarin based on the test results, while the control group (60 cases) implemented the conventional clinical warfarin medication strategy without genetic testing. Both groups were followed up for 6 months. The general clinical data, genotype distribution of the study group, INR attainment time, time in treatment range TTR, warfarin starting dose, maintenance dose, incidence of bleeding events and incidence of INR ≥ 4.0 events were compared between the two groups. Results The time to achieve INR in the study group was (9.56±1.68) d, which was significantly shorter than that in the control group (11.12±2.03) d, P<0.05. The TTR in the study group was (72.56±6.90) %, which was higher than that in the control group (64.45±7.82) %, P<0.05. The starting and maintenance doses of warfarin in the study group were (2.91±0.73) mg/d and (3.17±0.81) mg/d, respectively, which were not statistically different from those in the control group (P>0.05). There were six cases (20.00%) of small bleeding events in the study group, which was significantly lower than that in the control group (twenty-seven cases, 45.00%, P<0.05). In contrast, there was no significant difference in the incidence of major bleeding events between the two groups (P>0.05). The incidence of INR≥4.0 in the study group was 16.67%, significantly lower than that in the control group (40.00%, P<0.05). Conclusions Detection of VKORC1 and CYP2C9 polymorphisms in ICU patients with indication of anticoagulation is beneficial to enhance anticoagulation efficacy, reduce related adverse reactions, and improve drug safety.
关键词
重症监护室 /
华法林 /
基因多态性 /
CYP2C9 /
VKORC1 /
抗凝治疗
Key words
intensive care unit /
warfarin /
gene polymorphism /
CYP2C9 /
VKORC1 /
anticoagulation therapy
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