胺碘酮/华法林对CYP2C9和VKORC1分型患者抗凝作用的影响
|
摘要
为探讨合并使用胺碘酮和华法林对不同的CYP2C9和VKORC1分型患者的抗凝作用的影响,本研究选取2013年6月至2016年6月南华大学附属第一医院收治的应用华法林进行抗凝的患者380例作为研究对象,收集患者病例相关数据、合并用药情况及其他临床资料,根据基因检测,将患者分为CYP2C9和VKORC1型,由于基因位点的不同又将CYP2C9型患者分为CYP2C9*1*1(347例)和CYP2C9*1*3(33例),VKORC1型患者分为VKORC1-1639GG(7例)、VKORC1-1639GA(37例)和VKORC1-1639AA(336例)。将77例合并使用华法林和胺碘酮的患者与仅使用胺碘酮的患者进行临床指标对比,并探讨胺碘酮对不同CYP2C9和VKORC1分型患者使用华法林的稳定剂量及INR值的影响。研究显示,华法林合并使用胺碘酮的患者中有2例发生出血事件,出血发生率为2.60%;未合并使用胺碘酮的患者中有30例发生出血事件,出血发生率为9.90%,显著高于合并胺碘酮患者(p<0.05)。合并使用胺碘酮的患者和未合并使用胺碘酮的患者在性别、身高、体重、体表面积、是否吸烟等方面具有统计学差异(p<0.05);两组患者在年龄、糖尿病患者比例、高血压患者比例、血脂异常患者比例、基因型表现、华法林稳定剂量及INR值方面无统计学差异(p>0.05)。因此,短期观测时间内,胺碘酮不影响CYP2C9和VKORC1分型患者对华法林的抗凝作用。
In order to explore the effects of the amiodarone combined with warfarin on anticoagulation of different CYP2C9 and VKORC1 types of patients, the 380 patients, treated with warfarin for anticoagulation, from June2013 to June 2016 in The First Hospital Affiliated to Nanhua University, were taken as the research objects. The patients' case data, medication and other clinical data were collected. And the patients were divided into CYP2C9 and VKORC1 according to the results of gene detection. Because of different gene loci, the CYP2C9 patients were divided into CYP2C9*1*1(347 cases) and CYP2C9*1*3(33 cases), and VKORC1 patients were divided into VKORC1-1639GG(7 cases), VKORC1-1639GA(37 cases) and VKORC1-1639AA(336 cases). Compared the clinical index of 77 amiodarone and warfarin treated patients with that of the warfarin treated patients. Investigated the effects of amiodarone on the stabilizer and INR value of different CYP2C9 and VKORC1 patients treated with warfarin. The results showed that among the patients treated with warfarin and amiodarone, there were 2 cases of bleeding, and the bleeding rate was 2.60%; Among the patients treated with warfarin only, there were 30 cases ofbleeding, and the bleeding rate was 9.90%, significantly higher than the former(p<0.05). Among the patients who were treated with amiodarone & warfarin and patients who were treated with warfarin only, there were significant differences in gender, height, weight, body surface area and smoking(p<0.05), but no difference in age, the proportion of diabetes, hypertension, the proportion of abnormal blood lipid ratio, genotype, stabilizer content or INR value(p>0.05). Therefore, in the short term, amiodarone did not affect the anticoagulation of warfarin towards the CYP2C9 and VKORC1 patient.
In order to explore the effects of the amiodarone combined with warfarin on anticoagulation of different CYP2C9 and VKORC1 types of patients, the 380 patients, treated with warfarin for anticoagulation, from June2013 to June 2016 in The First Hospital Affiliated to Nanhua University, were taken as the research objects. The patients' case data, medication and other clinical data were collected. And the patients were divided into CYP2C9 and VKORC1 according to the results of gene detection. Because of different gene loci, the CYP2C9 patients were divided into CYP2C9*1*1(347 cases) and CYP2C9*1*3(33 cases), and VKORC1 patients were divided into VKORC1-1639GG(7 cases), VKORC1-1639GA(37 cases) and VKORC1-1639AA(336 cases). Compared the clinical index of 77 amiodarone and warfarin treated patients with that of the warfarin treated patients. Investigated the effects of amiodarone on the stabilizer and INR value of different CYP2C9 and VKORC1 patients treated with warfarin. The results showed that among the patients treated with warfarin and amiodarone, there were 2 cases of bleeding, and the bleeding rate was 2.60%; Among the patients treated with warfarin only, there were 30 cases ofbleeding, and the bleeding rate was 9.90%, significantly higher than the former(p<0.05). Among the patients who were treated with amiodarone & warfarin and patients who were treated with warfarin only, there were significant differences in gender, height, weight, body surface area and smoking(p<0.05), but no difference in age, the proportion of diabetes, hypertension, the proportion of abnormal blood lipid ratio, genotype, stabilizer content or INR value(p>0.05). Therefore, in the short term, amiodarone did not affect the anticoagulation of warfarin towards the CYP2C9 and VKORC1 patient.
引文
Chen X.Y.,and Peng Q.,2015,Correlation of CYP2C9 and VKORC1 polymorphisms with warfarin stable dose and computer model-predicted dose,Huazhong Keji Daxue Xuebao(Yixue Ban)(Journal of Huazhong University of Science and Technology(Health Sciences)),44(1):92-95(陈晓英,彭齐,2015,CYP2C9及VKORC1基因多态性对华法林稳态剂量和模型预测剂量的相关性研究,华中科技大学学报(医学版),44(1):92-95)
Chua Y.A.,Abdullah W.Z.,Yusof Z.,and Gan S.H.,2015,VKO-RC1 and CYP2C9 genotypic data-based dose prediction alone does not accurately predict warfarin dose requirements in some Malaysian patients,Turk.J.Med.Sci.,45(4):913-918
Duan W.Y.,Xu H.,and Ye Q.,2016,Verification and evaluation of genotype-guided warfarin maintenance dose prediction model for Chinese han population,Zhongguo Yaofang(China Pharmacy),27(11):1445-1450(管文燕,徐航,叶庆,2016,基因型指导我国汉族人群华法林稳定治疗剂量预测模型的验证及评价,中国药房,27(11):1445-1450)
El-Shmaa N.S.,El A.D.,and El F.W.,2016,The efficacy of pre-emptive dexmedetomidine versus amiodarone in preventing postoperative junctional ectopic tachycardia in pediatric cardiac surgery,Ann.Card.Anaesth.,19(4):614-620
Hou J.L.,Dong X.,and Wang Y.Q.,2015,Influence of genetic polymorphisms and non-genetic factors on the maintenance dose of warfarin,Zhonghua Yixue Yichuanxue Zazhi(Chinese Journal of Medical Genetics),32(5):629-634(侯江龙,董鑫,王玉庆,2015,非遗传因素与基因多态性对华法林临床用药稳定维持剂量的影响,中华医学遗传学杂志,32(5):629-634)
Khalighi K.,Cheng G.,Mirabbasi S.,Khalighi B.,Wu Y.,and Fan W.,2016,Linkage disequilibrium between the CYP2C19*2,*17 and CYP2C9*1 alleles and impact of VKORC1,CYP2C9,CYP2C19 gene polymorphisms and gene-gene interactions on warfarin therapy,J.Thromb.Thrombolysis.,
Topkara V.K.,Knotts R.J.,Jennings D.L.,Garan A.R.,Levin A.P.,Breskin A.,Castagna F.,Cagliostro B.,Yuzefpolskaya M.,Takeda K.,Takayama H.,Uriel N.,Mancini D.M.,Eisenberger A.,Naka Y.,Colombo P.C.,and Jorde U.P.,2016,Effect of CYP2C9 and VKORC1 gene variants on warfarin response in patients with continuous-flow left ventricular assist devices,Asaio J.,62(5):558-564
Wang F.F.,Chen Q.H.,and Fei Y.,2015,Analysis of clinical pharmacists participating in Hua Falin anticoagulation in patients with thrombocytopenia after double valve replacement,Zhongguo Yaolixue Tongbao(Chinese Pharmacological Bulletin),31(B11):41-42(王芳芳,陈秋红,费燕,2015,临床药师参与双瓣置换术后血小板减少患者华法林抗凝治疗的分析,中国药理学通报,31(B11):41-42
Wu X.Z.,Jiang L.P.,and Zhang L.,2015,Analysis of warfarin compliance in patients undergoing mechanical heart valve replacement,Zhongguo Linchuang Yaolixue Zazhi(The Chinese Journal of Clinical Pharmacology),31(9):696-698(吴西枝,姜丽萍,张林,2015,华法林心脏瓣膜术后抗凝的依从性研究,中国临床药理学杂志,31(9):696-698)
Yang L.M.,Wu Y.S.,Huang F.,Han T.,and Huang X.H.,2015,Influence of VKORC1-1639 G>A EENE polymorphisms on the bleeding complication risk of warfarin therapy in Chinese patients,Zhongguo Yaoxue Zazhi(Chinese Pharmaceutical Journal),50(11):978-982(阳丽梅,吴钰珊,黄烽,韩涛,黄旭慧,2015,VKORC1-1639G>A基因多态性对华法林出血并发症的影响,中国药学杂志,50(11):978-982)
Ye C.,Jin H.,Zhang R.,Sun Y.,Wang Z.,Sun W.,Sun W.,Peng Q.,Liu R.,and Huang Y.,2014,Variability of warfarin dose response associated with CYP2C9 and VKORC1 gene polymorphisms in Chinese patients,J.Int.Med.Res.,42(1):67-76
Yildirim E.,Erol K.,and Birdane A.,2015,Warfarin dose requirement in Turkish patients:the influences of patient charact eristics and polymorphisms in CYP2C9,VKORC1 and factor VII,Hippokratia,18(4):319-327
Zhang J.,Tian L.,Zhang Y.,and Shen J.,2015,The influence of VKORC1 gene polymorphism on warfarin maintenance dosage in pediatric patients:A systematic review and meta-analysis,Thromb.Res.,136(5):955-961
Zhang Y.T.,Lian g X.,Hu X.,Li K.X.,and Yang L.P.,2010,Rapid detection of warfarin-related gene of VKORC1 poly-morphisms of CYP2C9 based onthe ligase reaction,Zhong-guo Linchuang Yaolixue Yu Zhiliaoxue(Chin.J.Clin.Phar-macol.Ther.,),15(12):1395-1401(张亚同,梁欣,胡欣,李可欣,杨莉萍,2010,基于连接酶反应快速检测华法林相关基因VKORC1、CYP2C9多态性,中国临床药理学与治疗学,15(12):1395-1401)
Chua Y.A.,Abdullah W.Z.,Yusof Z.,and Gan S.H.,2015,VKO-RC1 and CYP2C9 genotypic data-based dose prediction alone does not accurately predict warfarin dose requirements in some Malaysian patients,Turk.J.Med.Sci.,45(4):913-918
Duan W.Y.,Xu H.,and Ye Q.,2016,Verification and evaluation of genotype-guided warfarin maintenance dose prediction model for Chinese han population,Zhongguo Yaofang(China Pharmacy),27(11):1445-1450(管文燕,徐航,叶庆,2016,基因型指导我国汉族人群华法林稳定治疗剂量预测模型的验证及评价,中国药房,27(11):1445-1450)
El-Shmaa N.S.,El A.D.,and El F.W.,2016,The efficacy of pre-emptive dexmedetomidine versus amiodarone in preventing postoperative junctional ectopic tachycardia in pediatric cardiac surgery,Ann.Card.Anaesth.,19(4):614-620
Hou J.L.,Dong X.,and Wang Y.Q.,2015,Influence of genetic polymorphisms and non-genetic factors on the maintenance dose of warfarin,Zhonghua Yixue Yichuanxue Zazhi(Chinese Journal of Medical Genetics),32(5):629-634(侯江龙,董鑫,王玉庆,2015,非遗传因素与基因多态性对华法林临床用药稳定维持剂量的影响,中华医学遗传学杂志,32(5):629-634)
Khalighi K.,Cheng G.,Mirabbasi S.,Khalighi B.,Wu Y.,and Fan W.,2016,Linkage disequilibrium between the CYP2C19*2,*17 and CYP2C9*1 alleles and impact of VKORC1,CYP2C9,CYP2C19 gene polymorphisms and gene-gene interactions on warfarin therapy,J.Thromb.Thrombolysis.,
Topkara V.K.,Knotts R.J.,Jennings D.L.,Garan A.R.,Levin A.P.,Breskin A.,Castagna F.,Cagliostro B.,Yuzefpolskaya M.,Takeda K.,Takayama H.,Uriel N.,Mancini D.M.,Eisenberger A.,Naka Y.,Colombo P.C.,and Jorde U.P.,2016,Effect of CYP2C9 and VKORC1 gene variants on warfarin response in patients with continuous-flow left ventricular assist devices,Asaio J.,62(5):558-564
Wang F.F.,Chen Q.H.,and Fei Y.,2015,Analysis of clinical pharmacists participating in Hua Falin anticoagulation in patients with thrombocytopenia after double valve replacement,Zhongguo Yaolixue Tongbao(Chinese Pharmacological Bulletin),31(B11):41-42(王芳芳,陈秋红,费燕,2015,临床药师参与双瓣置换术后血小板减少患者华法林抗凝治疗的分析,中国药理学通报,31(B11):41-42
Wu X.Z.,Jiang L.P.,and Zhang L.,2015,Analysis of warfarin compliance in patients undergoing mechanical heart valve replacement,Zhongguo Linchuang Yaolixue Zazhi(The Chinese Journal of Clinical Pharmacology),31(9):696-698(吴西枝,姜丽萍,张林,2015,华法林心脏瓣膜术后抗凝的依从性研究,中国临床药理学杂志,31(9):696-698)
Yang L.M.,Wu Y.S.,Huang F.,Han T.,and Huang X.H.,2015,Influence of VKORC1-1639 G>A EENE polymorphisms on the bleeding complication risk of warfarin therapy in Chinese patients,Zhongguo Yaoxue Zazhi(Chinese Pharmaceutical Journal),50(11):978-982(阳丽梅,吴钰珊,黄烽,韩涛,黄旭慧,2015,VKORC1-1639G>A基因多态性对华法林出血并发症的影响,中国药学杂志,50(11):978-982)
Ye C.,Jin H.,Zhang R.,Sun Y.,Wang Z.,Sun W.,Sun W.,Peng Q.,Liu R.,and Huang Y.,2014,Variability of warfarin dose response associated with CYP2C9 and VKORC1 gene polymorphisms in Chinese patients,J.Int.Med.Res.,42(1):67-76
Yildirim E.,Erol K.,and Birdane A.,2015,Warfarin dose requirement in Turkish patients:the influences of patient charact eristics and polymorphisms in CYP2C9,VKORC1 and factor VII,Hippokratia,18(4):319-327
Zhang J.,Tian L.,Zhang Y.,and Shen J.,2015,The influence of VKORC1 gene polymorphism on warfarin maintenance dosage in pediatric patients:A systematic review and meta-analysis,Thromb.Res.,136(5):955-961
Zhang Y.T.,Lian g X.,Hu X.,Li K.X.,and Yang L.P.,2010,Rapid detection of warfarin-related gene of VKORC1 poly-morphisms of CYP2C9 based onthe ligase reaction,Zhong-guo Linchuang Yaolixue Yu Zhiliaoxue(Chin.J.Clin.Phar-macol.Ther.,),15(12):1395-1401(张亚同,梁欣,胡欣,李可欣,杨莉萍,2010,基于连接酶反应快速检测华法林相关基因VKORC1、CYP2C9多态性,中国临床药理学与治疗学,15(12):1395-1401)