摘要
目的探讨细胞色素P450氧化酶2C9(CYP2C9)、维生素K环氧化物还原酶复合体亚单位1(VKORC1)基因多态性在肺血栓栓塞症(PTE)患者华法林抗凝治疗中的应用效果。方法选取2017年1月至2020年6月河北医科大学第二医院收治的163例PTE患者作为研究对象,根据华法林用药方式不同分为研究组(82例)和对照组(81例),研究组患者根据CYP2C9、VKORC1基因类型计算华法林初始剂量进行治疗,对照组患者以常规3 mg/d为初始剂量进行治疗。比较两组患者华法林起始剂量、维持剂量、国际标准化比值(INR)首次达标时华法林总剂量和日平均华法林剂量,INR达标时间、INR检测次数、住院时间、总医疗费用,以及不良反应发生情况。结果研究组82例患者CYP2C9的基因型为*1/*1(*2CC/*3AA)野生型74例、*1/*3(*2CC/*3AC)突变型7例、*3/*3(*2CC/*3CC)突变型1例,VKORC1基因型为AA野生型67例、GA突变型12例、GG突变型3例。研究组华法林起始剂量、维持剂量、INR首次达标时华法林总剂量和日平均华法林剂量均明显少于对照组[(1.91±0.72)mg/d比(3.00±0.00)mg/d、(2.33±0.64)mg/d比(3.24±0.98)mg/d、(24.96±5.17)mg比(42.50±9.85)mg、(2.51±0.70)mg比(3.47±1.06)mg](P<0.01);研究组INR达标时间、住院时间明显短于对照组[(12.54±2.20)d比(15.03±2.62)d、(12.67±5.87)d比(15.82±6.41)d](P<0.01),INR检测次数及总医疗费用明显少于对照组[(3.23±0.66)次比(4.57±1.06)次、(1.24±0.37)万元比(1.57±0.34)万元](P<0.01)。两组总不良反应发生率比较差异无统计学意义(P>0.05)。结论以CYP2C9、VKORC1基因类型为指导计算华法林起始剂量,制订华法林个体化治疗方案,可有效减少华法林无效抗凝及过度抗凝。
Objective To investigate the application effect of cytochrome P450 proteins 2C9(CYP2C9)and vitamin K epoxide reductase complex 1(VKORC1)gene polymorphism in warfarin anticoagulation therapy for pulmonary thromboembolism(PTE).Methods A total of 163 patients with PTE admitted to the Second Hospital of Hebei Medical University between Jan.2017 and Jun.2020 were included,and were divided into a study group(82 cases)and a control group(81 cases)according to different warfarin administration methods.The study group received warfarin initial dose calculated according to CYP2C9 and VKORC1 gene types,and the control group received conventional 3 mg/d as initial dose.The initial dose of warfarin,maintenance dose,the time of international normalized ratio(INR)reaching the target,the total dose of warfarin when INR first reaching the target,the number of INR tests and the average daily warfarin dose,the length of hospital stay and the total medical expenses,as well as the adverse reactions,were compared between two groups.Results Among the 82 patients in the study group,there were 74 cases of CYP2C9 genotypes of*1/*1(*2CC/*3AA)wild type,7 cases of*1/*3(*2CC/*3AC)mutant,1 case of*3/*3(*2CC/*3CC)mutant,there were 67 cases of VKORC1 genotypes of AA wild type,12 cases of GA mutant,and 3 cases of GG mutant.The warfarin starting dose,maintenance dose,total dose and average daily warfarin dose when INR first reaching the target of the study group were significantly lower than those of the control group[(1.91±0.72)mg/d vs(3.00±0.00)mg/d,(2.33±0.64)mg/d vs(3.24±0.98)mg/d,(24.96±5.17)mg vs(42.50±9.85)mg,(2.51±0.70)mg vs(3.47±1.06)mg](P<0.01),the INR reaching time and hospitalization time were significantly shorter than those in the control group[(12.54±2.20)d vs(15.03±2.62)d,(12.67±5.87)d vs(15.82±6.41)d](P<0.01);INR test times and total medical expenses in the study group were significantly lower than those in the control group[(3.23±0.66)times vs(4.57±1.06)times,(12.4±3.7)thousand yuan vs(15.7±3.4)thousand yuan](P<0.01).There was no significant difference in the incidence of total adverse reactions between the two groups(P>0.05).Conclusion Using CYP2C9 and VKORC1 gene types as the guidance to calculate the starting dose of warfarin and develop the individualized warfarin treatment plan,can effectively reduce the ineffective anticoagulation and excessive anticoagulation of warfarin.
作者
宫小薇
袁雅冬
贡莹
田甜甜
康世威
GONG Xiaowei;YUAN Yadong;GONG Ying;TIAN Tiantian;KANG Shiwei(Department Two of Respiratory and Critical Care Medicine,the Second Hospital of Hebei Medical University,Shijiazhuang 050000,China)
出处
《医学综述》
CAS
2021年第14期2883-2887,共5页
Medical Recapitulate
基金
河北省医学科学研究重点课题计划(20170091)。
