基因检测指导心脏瓣膜置换术后华法林给药剂量的临床研究  

A clinical study of genetic testing to guide the dosing of warfarin after heart valve replacement

作　　者：张帆[1] 李晖[1] 李京倖[1] Zhang Fan;Li Hui;Li Jingxing(Department of Cardiac Surgery,Beijing Anzhen Hospital,Capital Medical University,Beijing 100029,China)

机构地区：[1]首都医科大学附属北京安贞医院心外科,100029

出　　处：《中华胸心血管外科杂志》2021年第12期737-740,共4页Chinese Journal of Thoracic and Cardiovascular Surgery

摘　　要：目的探讨VKORC1和CYP2C9基因检测对于主动脉瓣置换术后华法林给药剂量的指导作用。方法172例主动脉瓣置换术后接受华法林抗凝治疗的患者纳入对照组(86例)和基因检测组(86例)。基因检测组对VKORC1和CYP2C9基因的3个位点进行检测,并根据基因检测结果及美国食品药品管理局(FDA)推荐的华法林口服剂量表确定华法林初始剂量,对照组以3 mg/天作为初始剂量。分别于服药后连续监测国际标准化比值(INR),比较两组INR规定时间及出院3个月随访时INR的达标率以及各种不良反应发生率。结果基因检测组根据基因检测结果起始剂量服用3 mg/天为68例(79.1%),起始剂量服用1.5 mg/天为10例(11.6%),起始剂量服用6 mg/天为8例(9.3%)。术后服药第3天和第6天的基因检测组INR达标率分别为45.3%和73.3%,对照组分别为29.8%和58.3%(P<0.05)。基因检测组院内出现INR危机值报告率为2.3%,对照组为7.1%。术后3个月基因检测组和对照组的INR达标率分别为86.1%和83.1%。结论基因检测可能有助于指导心脏瓣膜置换术后华法林初始剂量的选择,并更快达到稳定剂量。Objective To explore the role of genetic testing of VKORC1 and CYP2C9 in determining the dosage of warfarin after aortic valve replacement.Methods A total of 172 patients receiving warfarin after aortic valve replacement were divided into a control group(86 cases)and an experimental(86 cases)group based on acceptance of genetic testing.In the experimental group,three loci of VKORC1 and CYP2C9 were tested by polymerase chain reaction-restriction fragment length polymorphism technique,and the initial dose of warfarin was determined based on the genetic testing results and warfarin oral-dose table recommended by U.S.Food and Drug Administration(FDA).In the control group,warfarin(3 mg/d)was used as the initial dose.The international normalized ratio(INR)of each patient was continuously monitored after medication.The percentages of patients meeting the target INR in the two groups at specific time points and at 3-month follow-up after discharge from the hospital were monitored,and the incidence of various adverse events was compared between the groups.Results Based on the results of genetic testing,68 patients received 3 mg/d(79.1%),10 patients received 1.5 mg/d(11.6%),and eight patients received 6 mg/d(9.3%)as the initial dosages of warfarin in the experimental group.The percentages of the patients meeting the target INR on the third and sixth day of postoperative medication were 45.3%and 73.3%,respectively,in the experimental group,and 29.8%and 58.3%,respectively,in the control group(P<0.05).The INR critical values during hospitalization occurred in 2.3%in the experimental group and in 7.1%in the control group,while the percentage of the patients meeting the target INR after 3 months was 86.1%in the experimental group and 83.1%in the control group.Conclusion Genetic testing may guide the selection of the initial dose of warfarin after heart valve replacement to rapidly achieve a stable dose.

关 键 词：心脏瓣膜置换术 抗凝 华法林 VKORC1 CYP2C9 

分 类 号：R654.2[医药卫生—外科学]