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学科主题: 药剂学
题名:
基于基因型检测的药学干预对住院患者应用华法林疗效和安全性的影响
其他题名: Effects of pharmaceutical intervention based on genotype detection on curative effect and safety in hospitalized patients receiving warfarin
作者: 向倩1; 母光妍1; 赵楠1; 周颖1; 崔一民1
关键词: 华法林 ; 基因型 ; 干预性研究 ; Warfarin ; Genotype ; Intervention studies
刊名: 药物不良反应杂志
发表日期: 2014
DOI: 10.3760/cma.j.issn.1008-5734.2014.05.002
期: 5, 页:259-263
收录类别: 中国科技核心期刊 ; CSCD
文章类型: Journal Article
摘要: 目的:探讨基于基因型检测的药学干预对住院患者应用华法林疗效和安全性的影响。方法收集2013年6月至2014年3月在北京大学第一医院住院并根据细胞色素P450(CYP)2C9*2、CYP2C9*3、维生素K环氧化物还原酶复合物1(VKORC1)G-1639A基因型检测结果调整华法林剂量患者(试验组)和2012年6至12月应用华法林但未进行基因型检测患者(对照组)的病历资料进行回顾性分析,比较2组患者的住院时间、服用华法林时间、国际标准化比值( INR)曾出现≥3.0者占比、华法林相关出血发生率、出院时INR和出院时华法林剂量,对试验组患者分析出院时华法林剂量与临床药师给予的华法林建议剂量的相关性,并分析试验组患者上述指标与基因型的相关性。结果试验组102例,男性62例,女性40例,年龄14~88岁,平均(63±16)岁。对照组140例,男性89例,女性51例,年龄21~85岁,平均(64±13)岁。原发疾病包括心房颤动、深静脉血栓、肺栓塞和肾静脉血栓等。2组患者年龄和性别分布差异均无统计学意义。试验组平均住院时间和服用华法林时间明显长于对照组[(16.7±8.4)d比(12.6±6.0)d,(13.2±8.2)d比(9.9±6.1)d,均P<0.001]。2组中INR≥3.0者占比、华法林相关出血发生率、出院时INR的差异均无统计学意义。试验组携带CYP2C9*1/*3者(7例)出院时华法林剂量低于携带CYP2C9*1/*1者(95例)[(1.79±0.57)mg/d比(3.12±1.13)mg/d,P=0.003];携带VKORC1-1639 GG者(1例)和VKORC1-1639GA者(20例)出院时华法林剂量均高于携带VKORC1-1639AA者(81例)[6.00、(3.55±1.63)mg/d 比(2.87±0.92) mg/d,P=0.002]。试验组INR≥3.0者住院时间和服用华法林时间均多于INR<3.0者[(24.7±10.9)d比(15.2±6.9)d,(21.8±10.9)d比(11.6±6.4)d,均P<0.001],出院时华法林剂量低于INR<3.0者[(2.50±1.02)mg/d 比(3.13±1.15)mg/d,P=0.042]。对照组INR≥3.0者住院时间与INR<3.0者差异无统计学意义,服用华法林时间多于INR<3.0者[(12.6±6.5)d 比(9.3±5.8) d,P=0.015],出院时华法林剂量低于INR<3.0者[(2.49±1.17)mg/d 比(3.11±0.99)mg/d,P=0.007]。试验组与对照组分别有8和14例患者出现粪潜血阳性、尿中红细胞值偏高、牙龈出血等,均未出现严重出血。对照组患者是否发生出血与住院时间和服用华法林时间显著相关( P=0.001、P=0.008),试验组是否发生出血与华法林疗效指标间均无相关性。结论基于基因型检测的药学干预可排除遗传因素对华法林药效的影响,可避免因反复调整剂量而延长的住院时间,对确定华法林维持剂量有积极作用,对安全性无影响。建议应用华法林抗凝治疗的患者均应行基因型检测。 Objective To explore the effects of pharmaceutical intervention based on genotype detection on curative effect and safety in hospitalized patients receiving warfarin. Methods The medical records of patients hospitalized in the Department of Cardiology,First Hospital of Peking University whose dosages of warfarin were adjusted according to the results of CYP2C9*2,CYP2C9*3,vitamin K epoxide reductase complex subunit ( VKORC1 )G-1639A genotype testing from June 2013 to March 2014 ( experimental group ) and the patients received warfarin but did not carry the genotype testing( control group)from June to December 2012 were collected and analyzed retrospectively. The length of hospital stay, administration time of warfarin,proportion of patients whose international normalized ratio(INR)≥3. 0 had happened,incidence of bleeding associated with warfarin,INR values and warfarin dosage on discharging were compared between the patients in the two groups. The correlation of warfarin dosage on discharging and the suggested dosage proposed by clinical pharmacist,the above-mentioned parameters and the genotype in the experimental group were analyzed. Results There were 102 patients in the experimental group comprised 62 male and 40 female with average age of(63 ± 16)years(14-88). There were 140 patients in the control group comprised 89 male and 51 female with average age of( 64 ± 13 ) years( 21-85 ). The patients'primary diseases included auricular fibrillation,deep vein thrombosis,pulmonary embolism and renal vein thrombus,etc. There were no statistically significant difference between age and sexual distinction in the 2 groups. The average length of hospital stay and average administration time of warfarin in patients in the experimental group were obviously longer than those in the control group[(16. 7 ± 8. 4)d vs.(12. 6 ± 6. 0)d,(13. 2 ± 8. 2)d vs. (9. 9 ± 6. 1)d,all P <0. 001]. There were no statistically significant difference of the proportion of INR≥3. 0,incidence of bleeding associated with warfarin,and INR values on discharging between the 2 groups. The warfarin dosage on discharging in patients carried CYP2C9*1/ *3 (7 cases)were lower than those in the patients carried CYP2C9*1/ *1(95 cases)in the experimental group [(1. 79 ± 0. 57)mg/d vs.(3. 12 ± 1. 13)mg/d,P=0. 003]. The warfarin dosage on discharging in patients carried VKORC1-1639 GG(1 case)and VKORC1-1639GA(20 cases)were more than those in the patients carried VKORC1-1639AA(81 cases)in the experimental group[6. 00,(3. 55 ± 1. 63)mg/d vs.(2. 87 ± 0. 92)mg/d,P=0. 002]. The length of hospital stay and administration time of warfarin in patients who INR≥3. 0 were longer than those in the patients who INR<3. 0[(24. 7 ± 10. 9)d vs. (15. 2 ± 6. 9)d,(21. 8 ± 10. 9)d vs.(11. 6 ± 6. 4)d,all P<0. 001]and the dosages of warfarin on discharging was lower than that in the patients who INR<3. 0 in the experimental group[(2. 50 ± 1. 02)mg/d vs. (3. 13 ± 1. 15)mg/d, P=0. 042]. In the control group,the difference of length of hospital stay between the patients who INR≥3. 0 and <3. 0 was no statistically significant,the administration time of warfarin in patients who INR≥3. 0 was longer that in the patients who INR <3. 0[(12. 6 ± 6. 5)d vs. (9. 3 ± 5. 8)d,P=0. 015],and the warfarin dosages on discharging was lower than that in the in the patients who INR <3. 0[(2. 49 ± 1. 17)mg/d vs. (3. 11 ± 0. 99)mg/d,P=0. 007]. The cases of fecal occult blood positive,slightly higher of red blood cell in the urine,and gingival bleeding were 8 and 14 in the experimental group and the control group,respectively. No severe bleeding was appeared in both groups. The bleeding was significantly correlated with the length of hospital stay and the administration time of warfarin in the control group(P=0. 001,P=0. 008). There was no correlation between bleeding and warfarin curative indexes in the experimental group. Conclusions The pharmaceutical intervention based on genotype detection can eliminate the effect of genetic factors on warfarin curative effect,avoid prolonging hospitalization caused by adjusting the dose repeatedly,and have a positive role in determination of warfarin maintenance dose. The pharmaceutical intervention has no effect on safety. It is suggested that the patient who receives warfarin anticoagulant therapy should do the genotype detection.
语种: 中文
原文出处: 查看原文
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内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/43920
Appears in Collections:北京大学第一临床医学院_药剂科_期刊论文

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作者单位: 1.100034北京大学第一医院药剂科
2.100034北京大学第一医院药剂科
3.北京大学药学院药事管理与临床药学系

Recommended Citation:
向倩,母光妍,赵楠,等. 基于基因型检测的药学干预对住院患者应用华法林疗效和安全性的影响[J]. 药物不良反应杂志,2014(5):259-263.
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