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非体外循环冠状动脉旁路移植术围手术期出血的遗传多态性。

Genetic Polymorphisms and Perioperative Bleeding in Off-Pump Coronary Artery Bypass Grafting Surgery.

机构信息

Department of Clinical Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, China.

Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.

出版信息

Ann Thorac Surg. 2021 Jul;112(1):116-123. doi: 10.1016/j.athoracsur.2020.08.024. Epub 2020 Oct 16.

Abstract

BACKGROUND

Clopidogrel use before coronary artery bypass graft surgery may increase risk for perioperative hemorrhage. The effect of genetic polymorphisms related to clopidogrel responses on bleeding during or after off-pump coronary artery bypass graft surgery is unknown.

METHODS

This prospective study included 206 coronary artery disease patients scheduled for off-pump coronary artery bypass graft surgery. Genotypes were determined using Sequenom MassARRAY system. Severe bleeding was defined by the universal definition of perioperative bleeding in cardiac surgery.

RESULTS

Patients carrying the ABCB1 3435 wild-type genotype (CC) had a higher risk of severe perioperative bleeding compared with patients carrying the variant genotype (CT or TT; 33.9% vs 16.5%, P = .009). Low baseline hemoglobin level (odds ratio 0.944; 95% confidence interval, 0.917 to 0.972; P < .001), low baseline estimated glomerular filtration rate (odds ratio 0.977; 95% confidence interval, 0.956 to 0.999; P = .041), discontinuing clopidogrel 5 days or less before surgery (odds ratio 2.458; 95% confidence interval, 1.044 to 5.786; P = .039), and the ABCB1 wild-type genotype (CC; odds ratio 2.941; 95% confidence interval, 1.250 to 6.944; P = .014) were independent risk factors for severe perioperative bleeding.

CONCLUSIONS

Patients carrying the ABCB1 wild-type genotype (CC) had a higher rate of severe perioperative bleeding compared with patients carrying the variant genotype (CT or TT). Discontinuation of clopidogrel 5 days or less before surgery and the ABCB1 wild-type genotype (CC) were independent risk factors for severe perioperative bleeding.

摘要

背景

在冠状动脉旁路移植术前使用氯吡格雷可能会增加围手术期出血的风险。与氯吡格雷反应相关的遗传多态性对非体外循环冠状动脉旁路移植术后或术后出血的影响尚不清楚。

方法

本前瞻性研究纳入了 206 例拟行非体外循环冠状动脉旁路移植术的冠心病患者。采用Sequenom MassARRAY 系统确定基因型。严重出血根据心脏手术围手术期出血的通用定义来定义。

结果

与携带变异基因型(CT 或 TT)的患者相比,携带 ABCB1 3435 野生型基因型(CC)的患者围手术期严重出血的风险更高(33.9%比 16.5%,P =.009)。基线低血红蛋白水平(比值比 0.944;95%置信区间,0.917 至 0.972;P <.001)、基线低估算肾小球滤过率(比值比 0.977;95%置信区间,0.956 至 0.999;P =.041)、术前停用氯吡格雷 5 天或更短(比值比 2.458;95%置信区间,1.044 至 5.786;P =.039)和 ABCB1 野生型基因型(CC;比值比 2.941;95%置信区间,1.250 至 6.944;P =.014)是严重围手术期出血的独立危险因素。

结论

与携带变异基因型(CT 或 TT)的患者相比,携带 ABCB1 野生型基因型(CC)的患者严重围手术期出血发生率更高。术前停用氯吡格雷 5 天或更短时间以及 ABCB1 野生型基因型(CC)是严重围手术期出血的独立危险因素。

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