通讯作者: 赵光辉, zgh2007lq@163.com

DOI：10.12201/bmr.202601.00045

The Short-term Anticoagulation Therapy after Autologous Arteriovenous Fistulas Surgery Guided Based on VKORC1 Gene Polymorphism

• 摘要：目的 探讨并验证维生素K环氧化物还原酶复合体亚基1(Vitamin K Epoxide Reductase Complex Subunit 1, VKORC1)基因多态性对自体动静脉内瘘(autogenous arteriovenous fistulas,AVF)术后患者短期抗凝治疗效果及出血风险的影响,旨在为AVF术后短期抗凝治疗提供个体化、精准的指导方案。方法 2022年3月~2024年11月期间,在金华市中心医院选取154例拟行AVF术的患者纳入研究,采用随机数表法分为观察组(76例)和对照组(78例),所有患者术后均接受短期抗凝治疗。在术前采集患者外周血样本,采用实时荧光定量PCR (Quantitative Real-time PCR, qRT-PCR)检测VKORC1基因位点多态性。观察组患者根据VKORC1基因型指导华法林用药,对照组患者则采用常规经验性抗凝治疗方案。密切监测两组患者在抗凝治疗期间的国际标准化比值(international normalized ratio,INR)变化、出血并发症的发生率,对比华法林使用剂量。结果 观察组76例患者中63例VKORC1-AA型(82.89%)、12例VKORC1-AG型(15.79%)、1例VKORC1-GG型(1.32%),对照组中有57例VKORC1-AA型(73.08%)、18例VKORC1-AG型(23.08%)、3例VKORC1-GG型(3.85%)。两组间VKORC1基因型多样性并无差异(χ2=2.743,P=0.290)。观察组INR达标时间短于对照组(4.18±0.82)d vs (5.00±0.38)d,华法林初始剂量(1.97±0.62)ng/d vs(3.23±1.01)ng/d和华法林维持剂量(2.41±0.38)ng/d vs(2.92±0.97)ng/d均小于对照组(P均＜0.001)。观察组小出血事件(15.79% vs 39.74%)和INR≥4.0事件发生率(10.53% vs 29.49%)低于对照组(P均＜0.05)。两组患者术后1年的持续通畅率(93.42% vs 92.31%、大出血事件发生率(1.32% vs 8.97%)均无差异(P均＞0.05)。结论 VKORC1基因多态性在AVF术后短期抗凝治疗中具有重要的指导意义。基于VKORC1基因多态性进行个体化抗凝治疗,能够显著提高抗凝治疗的有效性和安全性,降低出血风险。

  关键词： VKORC1基因多态性; 自体动静脉内瘘; 抗凝治疗; 国际标准化比值; 安全性

   

  Abstract: Objective: To explore and verify the influence of Vitamin K Epoxide Reductase Complex Subunit 1 (VKORC1) gene polymorphism on the short-term anticoagulation therapy effect and bleeding risk in patients after autogenous arteriovenous fistulas (AVF) surgery, aiming to provide individualized and precise guidance plans for short-term anticoagulation therapy after AVF surgery. Methods from March 2022 to November 2024, 154 patients who were scheduled to undergo AVF surgery in Jinhua Central hospital were studied and divided into the observation group (76 cases) and the control group (78 cases) by the random number table method. All patients received short-term anticoagulation therapy after the surgery. Peripheral blood samples of patients were collected before the surgery, and the polymorphism of the VKORC1 gene locus was detected by Quantitative Real-time PCR (qRT-PCR). Patients in the observation group were guided to take warfarin medication based on the VKORC1 genotype, while patients in the control group were treated with a conventional empirical anticoagulation therapy regimen. The changes of the international normalized ratio (INR) and the incidence of bleeding complications of the two groups during anticoagulation therapy were closely monitored and the dosage of warfarin was compared. Results Among the 76 patients in the observation group, 63 cases were of VKORC1-AA type (82.89%), 12 cases were of VKORC1-AG type (15.79%), and 1 case was of VKORC1-GG type (1.32%). In the control group, there were 57 cases of VKORC1-AA type (73.08%), 18 cases of VKORC1-AG type (23.08%), and 3 case of VKORC1-GG type (3.85%). There was no difference in the genotype diversity of VKORC1 between the two groups (χ2=2.743, P=0.290). The time for reaching the INR standard in the observation group was shorter than that in the control group (4.18±0.82) d vs (5.00±0.38) d. The initial dose of warfarin (1.97±0.62) ng/d vs (3.23±1.01) ng/d and the maintenance dose of warfarin (2.41±0.38) ng/d vs (2.92±0.97) ng/d were both lower than those in the control group. The incidences of minor bleeding events (15.79% vs 39.74%) and INR≥4.0 events (10.53% vs 29.49%) in the observation group were lower than those in the control group. There were no differences in the continuous patency rate (93.42% vs 92.31%) and the incidence of major bleeding events (1.32% vs 8.97%) 1 year after surgery between the two groups of patients (all P > 0.05). Conclusions The polymorphism of the VKORC1 gene has significant guiding significance in short-term anticoagulation therapy after AVF. Individualized anticoagulation therapy based on VKORC1 gene polymorphism can significantly enhance the effectiveness and safety of anticoagulation therapy and reduce the risk of bleeding.

  Key words: VKORC1 gene polymorphism; Autologous arteriovenous fistulas; Anticoagulant therapy; International normalized ratio; Safety

  提交时间：2026-01-15

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• 序号	提交日期	编号	操作
  1	2025-12-30	10.12201/bmr.202601.00045V1	下载

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