基于基因多态性的华法林个体化给药对老年心脏瓣膜置换术后并发症发生率的影响

doi:10.3969/j.issn.1007-3205.2025.01.004

河北医科大学学报 ›› 2025, Vol. 46 ›› Issue (1): 20-24.doi: 10.3969/j.issn.1007-3205.2025.01.004

基于基因多态性的华法林个体化给药对老年心脏瓣膜置换术后并发症发生率的影响

河北医科大学第一医院急诊科，河北石家庄 050031

出版日期:2025-01-25 发布日期:2025-01-22
作者简介:邢蓓蓓（1981-），女，河北石家庄人，河北医科大学第一医院医师，医学学士，从事心脏外科疾病诊治研究。
基金资助:
河北省医学科学研究重点课题计划(20160701)

Effect of individualized warfarin administration based on gene polymorphism on the incidence of complications after heart valve replacement in elderly patients

Department of Emergency, the First Hospital of Hebei Medical University, Shijiazhuang 050031, China

Online:2025-01-25 Published:2025-01-22

摘要/Abstract

摘要： 目的研究基于基因多态性的华法林个体化给药对老年心脏瓣膜置换术后并发症发生率的影响。
方法分别以2019年1—12月和2020年1—12月在我院接受治疗的患者作为研究组以及对照组各120例作为研究对象，对照组患者华法林治疗方案：起始剂量为3 mg/d，根据患者的临床症状以及并发症的发生情况调整药物的剂量为1.5~6 mg/d。研究组患者则在入组后，依据维生素K还氧化酶还原酶复合物1(vitamin K epoxide reductase complex subunit 1，VKORC1)以及细胞色素p450酶2C9（cytochrome P450 2C9，CYP2C9）的基因多态性，AA型患者的使用剂量为3 mg/d，GG型患者的使用剂量为6 mg/d，AG型患者的使用剂量为4.5 mg/d。比较2组患者的基因多态性、心血管事件发生情况、药代动力学指标以及并发症发生情况。
结果 2组VKORC1以及CYP2C9基因多态性差异无统计学意义(P＞0.05)。研究组国际标准化比值(international normalized ratio，INR)［(2.01±0.02) vs. (2.22±0.01)］(t=102.879，P＜0.001)、过度抗凝次数［(9.62±2.37)次 vs. (22.58±2.74)次］(t=39.188，P＜0.001)、华法林半衰期［(58.71±0.02) h vs. (61.99±0.03) h］(t=996.536，P＜0.001)、药峰时间［(2.71±0.02) h vs. (2.99±0.03) h］(t=85.070，P＜0.001)低于对照组，INR达标时间［(6.52±2.72) s vs. (4.89±2.33) s］(t=4.986，P＜0.001)、清除率［(138.01±11.02) mL/h vs. (112.22±11.25) mL/h］(t=17.940，P＜0.001)、最高血药浓度［(621.29±11.92) μg/L vs. (607.78±11.94) μg/L］(t=8.772，P＜0.001)高于对照组。研究组患者皮肤紫癜(χ2=4.655，P=0.031)、牙龈出血(χ2=7.211，P=0.007)、鼻腔出血(χ2=5.661，P=0.017)发生率低于对照组。
结论基于基因多态性的华法林个体化给药可有效降低老年心脏瓣膜置换术后并发症发生率，建议临床推广。

关键词: 心脏瓣膜假体植入, 华法林, 基因多态性

Abstract: Objective To investigate the effect of individualized warfarin administration based on gene polymorphism on the incidence of complications after heart valve replacement in elderly patients.
Methods Patients treated in our hospital from January to December 2019 and from January to December 2020 were selected as the research group (n=120) and another 120 patients served as the control group. The warfarin treatment plan for patients in the control group was as follows: the initial dose of warfarin was 3 mg/d, and the dose of warfarin was adjusted to 1.5-6 mg/d according to the clinical symptoms and complications of patients. After enrollment, the research group received a dose of 3 mg/d for AA type patients, 6 mg/d for GG type, and 4.5 mg/d for AG type based on the gene polymorphisms of vitamin K epoxide reductase complex subunit 1(VKORC1) and cytochrome p450 2C9 (CYP2C9). Gene polymorphism, incidence of cardiovascular events, pharmacokinetic indexes and complications were compared between the two groups.
Results There was no significant difference in VKORC1 and CYP2C9 gene polymorphisms between the two groups (P＞0.05). International normalized ratio (INR) ［(2.01±0.02) vs. (2.22±0.01)］ (t=102.879, P＜0.001), times of excessive anticoagulation ［(9.62±2.37) vs. (22.58±2.74)］ (t=39.188, P=0.001), half-life of warfarin ［(58.71±0.02) h vs. (61.99±0.03) h］ (t=996.536, P＜0.001), and the peak time ［(2.71±0.02) h vs. (2.99±0.03) h］ (t=85.070, P=0.001) were lower in the research group than in the control group, while INR standard time ［(6.52±2.72) s vs. (4.89±2.33) s］ (t=4.986, P＜0.0.001), the clearance rate ［ (138.01±11.02) mL/h vs. (112.22±11.25) mL/h］ (t=17.940, P＜0.001), and the highest blood drug concentration ［(621.29±11.92) μg/L vs. (607.78±11.94) μg/L］ (t=8.772, P＜0.001) were higher than those in the control group. The incidence of skin purpura (χ2=4.655, P=0.031), gingival bleeding (χ2=7.211, P=0.007) and nasal bleeding (χ2=5.661, P=0.017) in the research group was lower than that in the control group.
Conclusion The individualized administration of warfarin based on gene polymorphism can effectively reduce the incidence of complications after heart valve replacement in the elderly, and it is recommended to be popularized in clinical practice.

Key words: heart valve prosthesis implantation, warfarin, gene polymorphism

邢蓓蓓, 申红, 王巍, 刘璞娟. 基于基因多态性的华法林个体化给药对老年心脏瓣膜置换术后并发症发生率的影响 [J]. 河北医科大学学报, 2025, 46(1): 20-24.

XING Bei-bei, SHEN Hong, WANG Wei, LIU Pu-juan. Effect of individualized warfarin administration based on gene polymorphism on the incidence of complications after heart valve replacement in elderly patients [J]. Journal of Hebei Medical University, 2025, 46(1): 20-24.

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基于基因多态性的华法林个体化给药对老年心脏瓣膜置换术后并发症发生率的影响

Effect of individualized warfarin administration based on gene polymorphism on the incidence of complications after heart valve replacement in elderly patients

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