ObjectiveTo investigate the effect of CYP2C9 and APOE on the dose of stable warfarin and model prediction in Hainan population.MethodsFrom August 2016 to July 2018, 368 patients who required heart valve replacement and agreed to take warfarin anticoagulation at the second department of cardiothoracic surgery in our hospital were enrolled, including 152 males aged 48.5–70.5 (60.03±10.18) years and 216 females aged 43.5–65.6 (54.24±11.35) years. CYP2C9 and APOE were amplified by polymerase chain reaction. The gene fragment was sequenced by the Single Nucleotide Polymorphisms (SNP) site. The patients' age, sex, weight, history of smoking and drinking, and the dose of stable warfarin were recorded. Regression analysis of these clinical data was made to construct a dose prediction model.ResultsAmong 368 patients, CYP2C9 genotype test results showed 301 patients (81.8%) with *1*1 genotype, and 67 patients (18.2%) with *1*3 type. For different CYP2C9 genotype patients, the difference was statistically significant in the dose of stable warfarin (P<0.05). The results of APOE genotype showed 93 patients (25.3%) with E2 genotype, 221 patients (60.1%) with E3 genotype, and 54 patients (14.7%) with E4 genotype; the dose of stable warfarin in patients with different APOE genotypes was statistically significant (P<0.05). Multiple regression analysis showed that patients' age, body weight, and CYP2C9 and APOE genotypes were correlated with the dose of stable warfarin. The correlation coefficient R2 was 0.572, and the prediction model was statistically significant (P<0.05).ConclusionCYP2C9 and APOE gene polymorphisms exist in Hainan population. There is significant difference in the dose of stable warfarin among different genotypes of patients. The model to predict stable warfarin can partly explain the difference of warfarin among different patients.
ObjectiveTo clarify the relationship between the G/C polymorphism of inflammatory gene matrix metalloproteinase-2 (MMP2) and warfarin therapy after cardiac valve replacement (CVR). MethodsWe finally identified 96 patients who received additional warfarin therapy after CVR as a trial group and 78 patients without the warfarin therapy as a control group. Gene sequencing techniques were adopted to determine single nucleotide polymorphism allele. We analyzed genotype and clinical features of the two groups and explored the relationship between the different MMP2 geno-types and warfarin therapy after CVR. Logistic regression was used to analyze the correlation between genotypes and risk factors after CVR and Kaplan-Meier survival curves were performed to analyze the survival time and efficacy of patients carrying MMP2 GC and GG genotypes. ResultsThe distribution of MMP2 genotype in patients receiving warfarin therapy after surgery was different from that in patients without warfarin therapy. The results of multivariate logistic regression analysis showed that GC and GG genotypes were risk factors of complications of CVR. The proportion of GG genotype was higher in the patients with postoperative complications compared with those without. The survival time of patients carrying genotype MMP2 GG was shorter than those carrying GC genotype (P < 0.05), which reveals that the level of MMP2 GG genotype was associated with the prognosis. ConclusionG allele of MMP2 is a risk factor of complications following CVR. GG genotype is relevant to CVR and prognosis, which can be regarded as a risk factor post CVR.
ObjectivesTo compare different formula calculated dosages with the actual doses of warfarin from patients in Beijing Hospital so as to investigate suitable warfarin dosing models for Chinese patients.MethodsOne hundred and three Chinese patients with long-term prescription of warfarin were randomly selected from Beijing Hospital from July 2012 to May 2013. The CYP2C9 and VKROC1 genotypes and basic statistical information were collected. SPSS 18.0 software was used to compare the differences between different formula calculated dosages and the actual dosages of warfarin.ResultsFive genotypes were found in 103 patients, including: CYP2C9 AA genotype + VKORC1 AA genotype (n=72, 69.9%), CYP2C9 AA genotype + VKORC1 AG genotype (n=17, 16.5%), CYP2C9 AC genotype + VKORC1 AA genotype (n=10, 9.7%), CYP2C9 AC genotype + VKORC1 AG genotype (n=3, 2.9%) and CYP2C9 AA genotype + VKORC1 GG genotype (n=1, 1%). Compared with the actual dosages of warfarin, the degree of coincidence was highest for dosages calculated by Jeffrey’s formula.Conclusions Using Jeffrey’s formula to calculate warfarin dosages may be more suitable for Chinese patients with using long-term warfarin. Due to limited sample size, prospective and large sample size studies are required to verify the above conclusion.
Objective To investigate the role of clinical pharmacists in warfarin therapy. Methods A total of 134 patients underwent prosthetic heart valve replacement and had warfarin for life from March 2013 to October 2013 in Fujian Medical University Union Hospital. All patients were equally divided into two groups (an intervention and a non-intervention group) crosswise by sequence. There were 67 patients in each group. The anticoagulant effects of the two groups were compared. Results There was no statistical difference in the patients' demographic information between the two groups. However, the time for the patients to reach the target international normalized ratio(INR) values for the first time (7.1±3.3 dvs. 10.5±5.0 d,P=0.000) and time of INR in the therapy range (46.3%±18.8%vs.19.0%±16.2%,P=0.000) during their hospitalization, proportion of time of under anticoagulation (47.5%±19.5%vs. 71.2%±22.9%,P=0.000), proportion of time of anticoagulation overdose (5.3%±8.2%vs. 9.9%±16.7%,P=0.002) were significantly different. While there was no statistical difference in postoperative hospitalization time between the two groups (19.9±6.6 dvs. 18.1±7.0 d,P=0.137). There were 4 patients (6.0%) with minor hemorrhage and no severe complication was found in the intervention group. There were seven patients (10.4%) with mild hemorrhage, two patients with stroke, one patient with mild pulmonary embolism, and severe complication rate of 4.5% in the non-intervention group. Conclusion With clinical pharmacists involved in the whole anticoagulation therapy progress of patients after mechanical heart valve replacement, the time to achieve the therapeutic window for the first time is effectively shorten, and the time of the INR value controlled in therapeutic range is highly improved during hospitalization time. Moreover, the patients' risk of thrombosis and bleeding is eventually reduced.
ObjectiveTo verify the reliability of Anticlot Assistant, a patient self-management system for warfarin therapy assisted by artificial intelligence.MethodsIt was a single-center, prospective cohort study. The eligible 34 participants were recruited consecutively between November 29, 2017 to September 27, 2018 and managed by warfarin therapy via Anticlot Assistant. The recommendations of Anticlot Assistant were examined and verified by the doctors to ensure the security. Medical records were exported from the the background management system. An univariate analysis compared the outcomes between accepted and overridden records and a logistic regression model was built to determine independent predictors of the outcomes. The research team analyzed 153 medical records, which were from 18 participants and were input by 19 doctors. There were 97 records with doctor accepting the suggestion and 56 records with doctor rejecting the suggestion .ResultsWhen the doctors accepted the recommendations, the percentage of the next-test international normalized ratio (INR) in the therapeutic range was higher (64.95% vs. 44.64%, RR=2.298, 95%CI 1.173 to 4.499, P=0.014). The logistic regression analysis revealed that accepting the recommendations was an independent predictor for the next-test INR being in the therapeutic range after controlling potentially confounding factors (OR=2.446, 95%CI 1.103 to 5.423, P=0.028).ConclusionThe algorithm of Anticlot Assistant is reasonable and reliable.
ObjectiveTo compare the cost-effectiveness of warfarin and enoxaparin overlapping treatment for the prevention of venous thromboembolism (VTE) or pulmonary embolism (PE) in patients with nephrotic syndrome (NS). MethodsA decision tree model was constructed. The efficacy data applied in our decision tree were from clinical data, and the cost data was based on the hospitalization cost of 103 patients with nephrotic syndrome in Guangdong Provincial People's Hospital from 2013 to 2014, State Development and Reform Commission pricing and literature report. The one-way sensitivity analyses was conducted to analyze the stability of test. ResultsIn base case, the cost and cost-effective ratio of warfarin and enoxaparin overlapped treatment for 3 days were 10305.49 yuan and 31607.15, respectively. While those overlapped treatment for 4 days were 8849.36 yuan and 20896.46, overlapped treatment for 5 days and above were 9494.29 yuan and 21659.95, respectively. The incremental cost-effectiveness ratio of 4 days versus 5 days and above was 5600.96. The cost-effective ratio of 4 days was lower but the incremental cost-effectiveness ratio of it was higher. The sensitivity analysis showed the test result was stable. ConclusionCost-effectiveness analysis shows that warfarin and enoxaparin overlapping treatment for 4 days in patients with nephrotic syndrome has cost-effective advantage. Due to the limited sample size of our study, the above conclusion should be proved by more large-scale high-quality clinical studies.
Warfarin is one of the most frequently prescribed oral anticoagulant. Many researches have shown that the genotypes have been strongly associated with warfarin maintenance doses. Especially, it has been accepted in academia that cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex 1 subunit (VKORC1) could affect the warfarin maintenance doses. There are also many other genotypes that were reported to be related to warfarin doses, but the results have been in controversial so far. The studies found that the dose formula which contained the genetic factors and clinical information could accurately predict the maintenance dose of warfarin, however, its usefulness is suspected due to the inconsistent results of clinical trials. Large-sample and multi-center studies are necessary to verify the specific effects of gene and non-gene factors to warfarin dose; at the same time, testing constructed models or building new models help to improve the explained percentages of individual differences.
Objective To investigate the influence of CYP2C9 3，VKORC1-1639 G＞A and CYP4F2 rs2108622 genetic polymorphisms on warfarin dosages of patients after heart valve replacement. Methods A total of 133 patients undergoing heart valve replacement in the Department of Cardiovascular Surgery of Fujian Provincial Hospital from November 2011 to August 2012 were included in this study. Polymerase chain reaction（PCR）gene sequencing was performed to detect CYP2C9 3，VKORC1-1639 G＞A and CYP4F2 rs2108622 genetic polymorphism of these 133 patients. Patients were grouped according to their genotypes，and average warfarin dosages were compared between different genotype groups. Results The frequencies of CYP2C9 3 AA，AC and CC were 127 patients，6 patients and 0 patient respectively，and average daily warfarin dosages were 3.75 mg and 2.13 mg respectively which were statistically different between differentCYP2C9 3 genotypes （P＜0.05）. The frequencies of VKORC1-1639 G＞A GG，GA and AA were 3 patients，32 patientsand 98 patients respectively，and average daily warfarin dosages were 6.00 mg，4.50 mg and 3.00 mg respectively which were statistically different between different VKORC1-1639 G＞A genotypes （P＜0.05）. The frequencies of CYP4F2 rs 2108622 CC，CT and TT were 67 patients，59 patients and 7 patients respectively，and average daily warfarin dosages were 3.00 mg，3.75 mg and 4.50 mg respectively which were statistically different between different CYP4F2 rs2108622 genotypes（P＜0.05）. Conclusion CYP2C9 3，VKORC1-1639 G＞A and CYP4F2 rs2108622 genetic polymorphisms are associated with individual difference of warfarin dosages of patients after heart valve replacement.
Objective To explore clinical effect and safety of rivaroxaban in treatment of acute pulmonary thromboembolism at moderate risk with deep vein thrombosis of lower limbs. Methods The clinical data of 60 patients with acute pulmonary thromboembolism at moderate risk with deep vein thrombosis of lower limbs, collected from January 2010 to March 2017 in Hunan Provincial People’s Hospital, were retrospectively analyzed. According to the different treatment, these patients were randomly divided into a rivaroxaban group and a control group (traditional warfarin anticoagulation), with 30 patients in each group. The clinical effect and safety were compared between two groups on the 10th day, 20th day and 30th day after treatment. Results Compared with the control group, maximum short axis diameter, ratio of right and left ventricles, systolic pulmonary artery pressure, and main pulmonary artery diameter measured by CTPA and echocardiography in the rivaroxaban group were not significantly different on the 10th day, 20th day and 30th day after treatment. However, the intragroup differences were statistically significant at different timepoint (P<0.05). Levels of N-terminal-pro-brain natriuretic peptide of two groups after treatment were significantly reduced on the 10th day, 20th day and 30th day after treatment, and the values of PO2 were significantly increased on the 10th day and 20th day after treatment (P<0.05), but no significant differences were found in the values of PO2 on 20th day and 30th day after treatment. D-dimer in the two groups was obviously increased on the 10th day after treatment but significantly declined on the 20th day and 30th day after treatment (all P<0.05). These changes were predominant in the rivaroxaban group. Conclusion Rivaroxaban is effective and safe for acute pulmonary thromboembolism at moderate risk with deep vein thrombosis of lower limbs, and worthy of clinical implementation and application.
ObjectiveTo study the correlation between international normalized ratio (INR) and coagulation factor Ⅱ and Ⅹ in patients with pulmonary thromboembolism treated with warfarin at moderate and low intensity anticoagulation.MethodsFifty-one patients with pulmonary thromboembolism treated with warfarin orally were divided into low-intensity anticoagulation group (INR from 1.6 to 2.0) and standard-intensity anticoagulation group (INR form 2.0 to 3.0) according to their monitoring INR indices. The levels of coagulation factor Ⅱ and Ⅹ were measured, and the correlation between INR level and coagulation factor activity was compared.ResultsThe INR of the low intensity anticoagulation group was 1.69±0.2 and the standard intensity anticoagulation group was 2.55±0.46. The corresponding activity of coagulation factor Ⅱ was (48.3±28.0)% and (24.0±8.0)% respectively. The activity of coagulation factor Ⅹ was (32.8±24.0)% and (16.7±6.0)%. There was a negative correlation between the activity of INR and coagulation factor Ⅱ and Ⅹ, with correlation coefficients of –0.903 and –0.459, respectively. Coagulation factor Ⅱ activity < 40%, coagulation factor Ⅹ activity inhibitory level < 25% is defined as anticoagulation effect. When coagulation factor Ⅱ activity level reaches anticoagulation effect, the corresponding minimum INR value was 1.56 and as to coagulation factor Ⅹ, the corresponding minimum INR value was 1.66.ConclusionsINR is negatively correlated with the activity of coagulation factor Ⅱ and coagulation factor Ⅹ. With the increase of INR, the activity of coagulation factor Ⅱ and coagulation factor Ⅹ decrease. Low intensity anticoagulation could not effectively inhibit the activity of coagulation factor.