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VKORC1 And CYP2C9 Genetic Polymorphisms:A Comprehensive Intervention On Warfarin Usage

Posted on:2018-02-13Degree:MasterType:Thesis
Country:ChinaCandidate:X GuFull Text:PDF
GTID:2334330515957022Subject:Pharmacology
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Objective1 According to the non-genetic factors of warfarin anticoagulation including gender,age,height,weight,body surface area(BSA),smoking,drinking,diet,medication,and the related genetic variation factors(include CYP2C9 and VKORC1)in Chinese Han patients,this study aimed to establish a warfarin stable dose algorithm in a cohort of Chinese Han patients.2 To investigate the factors that affect patients' adherence of warfarin application in anticoagulation,including patients' understanding and satisfaction of their treatments.To observe the dynamic changes of patient adherence,cognition,satisfaction,after multiple patient education.And investigate the relationship between the incidences of adverse reactions and patients' adherence.Method1 Patients after cardiac valve replacement and with warfarin for the first time were collected.RT-PCR method was applied to detect the polymorphisms of VKORC1-1639?CYP2C9.The international normalized ratio(INR)values,warfarin dose were recorded.When patients' INR value in the target range for more than 4 times while taking the same dose of warfarin,the dose were recorded.We want to analyze the correlation between the stable dose and the various factors and to establish a warfarin stable dose algorithm with multiple regression analysis.2 Asophisticated research was conducted on patients of an anticoagulation clinic who had long-term usage of warfarin.Questionnaires,including the 8-Item Morisky Medication Adherence Scale(MMAS-8)for patients' adherence,the 9-Item Treatment Satisfaction Questionnaire for Medication(TSQM-9)for patients' satisfaction,an evaluation form designed based on guidelines and instructions of warfarin for patients' understanding were conducted.After the baseline survey,the patients were.followed up for the first,third and sixth months.Percentage of time within the therapeutic range was based on four times of INR to determine anticoagulation control,the incidence adverse reaction were also recorded.Result1 Among 150 cases of Chinese Han patients after cardiac valve replacement,VKORC1-1639AA:120 cases(80%),VKORC1-1639AG mutation type:29 cases(19.33%),VKORC1-1639GG mutation type:1 cases(0.67%).CYP2C9*2 mutation,only 1 cases(0.67%)patients with CYP2C9*1/*2 mutant is rare in this study.Wild type CYP2C9*1/*1:140 cases(93.33%),CYP2C9*1/*3 mutant:9 cases(6%);CYP2C9*3/*3 mutant:1 cases(0.67%).Carrying the mutant VKORC1-1639G gene need significantly more warfarin than patients with type VKORC1-1639AA(P<0.001),carrying the mutant CYP2C9*3 gene need significantly lower warfarin dose than patients with type CYP2C9*1/*1(P<0.001).We found that age and body surface area are predictors of the stable dose of warfarin,gender,height,weight,BMI,smoking,drinking,diet were excluded.Using stepwise regression analysis to establish the algorithm:In Dose(mg/d)= 0.248-0.574*CYP2C9*1/*3 or*3/*3+0.406*VKORC1-1639GA or GG+0.373*BSA-0.004*age.2 A total of 132 patients participated in this research.The MMAS-8 score of patients'adherence was 4.87± 1.27,the TSQM-9 score of patients' satisfaction was 60.33±9.66,and the evaluated score of patients' understanding was 4.38 ± 2.48.Both patients' satisfaction and understanding show positive correlations with patients' adherence(r equals 0.649 and 0.651 respectively;P<0.01);and patients with higher degrees of education or lived in urban areas tended to have higher adherence of warfarin application.The score of cognition,satisfaction and adherence increased between each investigate.The score increased fast especially between the baseline and the first month and then gradually slowed down.The ratio of INR within the therapeutic range and the incidence of adverse reactions were closely related to adherence(P<0.001).Conclusion1 VKORC1 and CYP2C9 are important factors to predict warfarin stable dose;age,body surface area is larger than the non genetic factors.This warfarin stable dose algorithm can explain 45.5%patients' dose variants.2 Patients' adherence of warfarin application at discharge was still low.Patients' adherence was closely related to the cognition and satisfaction,and the adherence had a significant influence on the ratio of INR within the therapeutic range and the incidence of adverse reactions.After many times of medication education,patients' cognition,satisfaction and adherence increased,the first time of medication education effect is the most obvious.3 Pharmaceutical intervention helps achieve warfarin individualized treatment,awareness,satisfaction and compliance of patients with anticoagulation therapy can effectively improve the coagulation function,improve compliance rate,and reduce the risk of bleeding and other adverse reactions.
Keywords/Search Tags:Warfarin, CYP2C9, VKORC1, Genetic polymorphism, Comprehensive intervention
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