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.
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 explore the anticoagulant strategy of adjusting the dose of warfarin at different stages after mechanical valve replacement of mitral valve.MethodsClinical data of a total of 302 patients, including 76 males and 226 females, with an average age of 50.1±10.1 years, who underwent mechanical mitral valve replacement in the Chinese adult cardiac surgery database from 2013 to 2017 were retrospectively analyzed. According to the dose adjustment strategy of taking warfarin, the patients were divided into a D group (adjusting warfarin dose in days) and a W group (adjusting warfarin dose in weeks) to evaluate the anti-coagulation effect of warfarin.ResultsThe total follow-up time was 423277 d (1159.7 years). There was no significant difference in the overall anticoagulant strength, and the warfarin dose adjusted in days was better in the early postoperative period (P<0.05), especially in patients over 60 years. It was better to adjust warfarin dose in weeks in the middle and long periods (P<0.05), especially in patients ≤40 years. In terms of the stability of anticoagulation, it was better to adjust the dosage of warfarin in weeks (P<0.05). It was better to adjust the dosage of warfarin in weeks for early, middle- and long-term anticoagulant therapy after operation (P<0.05), especially in the females aged >40 and ≤50 years.ConclusionWithin the target range of international normalized ratio (1.5-2.5), the anticoagulant strategy of adjusting warfarin dose in days after mechanical valve replacement of mitral valve can achieve a better anticoagulant strength, and adjusting the dosage of warfarin in weeks is better in the middle- and long-term after operation. In general, the anticoagulant effect is more stable in the short term when warfarin dose is adjusted on a weekly basis.
Warfarin is one of the most frequently prescribed oral anticoagulant. Many researches have shown that the cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex 1 (VKORC1) genotypes have been strongly associated with warfarin maintenance doses. Warfarin maintenance doses can be accurately predicted by use of dosing algorithms including genetic and clinical information. Although several clinical trials demonstrated mixed results, calling into question the utility of this approach. The present data do not support genetic testing to guide warfarin maintenance doses, but in the setting where genotype data are available, use of this approach is reasonable. Ongoing trials are expected to provide more data, and more work is needed to define dosing algorithms that include appropriate variables in minority populations. All these work will further improve the clinical application of genotype-guided warfarin maintenance doses.
Objective To evaluate the long-term anticoagulation outcomes of target international normalized ratio (INR) 1.60 to 2.20 and weekly dosage adjustment of warfarin in patients after mechanical heart valve replacement. Methods Outpatients after mechanical heart valve replacement at least 6 months were registered continually from July 2011 to July 2016 in department of cardiothoracic surgery at Zigong No.4 People's Hospital and West China Hospital. There were 1 690 females (70.62%) and 703 males (29.38%) with a median age of 47 years, ranging from 14 to 80 years. All patients were followed up for 6-61 months. Target INR was 1.60 to 2.20 and warfarin dosage were adjusted weekly. Unexpected bleeding, thrombogenesis and thromboembolism, time in therapeutic range (TTR) and fraction of TTR (FTTR) were recorded and calculated to evaluate the outcome of anticoagulation management. Results A total of 2 393 patients with 26 521 INR values were included for data analysis. INR values varied from 0.90-8.39 (1.82±0.45) and required weekly doses of warfarin were 1.75-61.25 (21.72±7.39) mg. TTR of target INR and acceptable INR was 59.38% (1 449 514.0 days/2 441 060.0 days) and 73.57% (1 795 971.0 days/2 441 060.0 days), respectively. FTTR of target INR and acceptable INR were 50.71% (13 450 times/26 521 times), 65.25% (17 305 times/26 521 times). During the follow-up , anticoagulation-related complications included: cerebral infarction in 21 patients (complete recovery in 18 patients, physical activity disorder in 3 patients), cerebral hemorrhage in 4 patients (death in 1 patient, complete recovery in 3 patients), severe gastrointestinal bleeding in 3 patients (completely recovered) and uterine bleeding in 1 patient (surgical removal of the uterus). Conclusion Target INR 1.60–2.20 and warfarin weekly dosage adjustment for patients after mechanical heart valve replacement is reasonable and safe.
Objective To explore the impact of the women taking warfarin throughout pregnancy after mechanical valve replacement on the children’s physical and mental development.Methods A total of 12 children whose mothers had taken mechanical valve replacement before pregnancy were enrolled in the experimental group in this study, for determination of their physical and mental development. The following indicators were measured: a) Physical development indexes: height, weight, sitting height, head circumference, chest circumference; b) Mental development indexes: intelligence quotient (IQ), and development quotient (DQ) which included adaptability, big movement, fine motor, language, and individual-society. According to the 1?∶?2 matching ratio, 24 children of the healthy women were selected in the control group, and then the difference of each index between the two groups was analyzed. Results In the aspects of both physical development indexes and mental development indexes, there were no significant differences in the children aged 0 to 3 yrs, 4 to 6 yrs, and 6 to 12 yrs in the two groups (Pgt;0.05). Conclusion After mechanical valve replacement, women taking oral anticoagulant warfarin in daily dose not exceeding 5mg are safe, and there are no negative effects on children’s physical and mental development.
ObjectivesTo investigate the correlation of warfarin dose genetic and polymorphism of Han-patients after heart valve replacement, to forecast the anticoagulation therapy with warfarin reasonable dosage, and to realize individualized management of anticoagulation monitoring. MethodsWe selected 103 patients between January 1, 2011 and December 31, 2012 in West China Hospital of Sichuan University who were treated by oral warfarin after heart valve replacement with monitoring anticoagulation by international normalized ratio (INR) in Anticoagulation Therapy Database of Chinese Patients after Heart Valve Replacement. There were 32 males and 71 female at age of 21-85 (48.64± 11.66) years. All the patients' CYP2C9 and VKORC1 genetic polymorphisms were detected by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RELP) method and gene sequencing technology. Warfarin concentration in plasma was determined by high performance liquid chromatography (HPLC) method. The activity of coagulation factorⅡ, Ⅶ, Ⅸ, Ⅹwas determined by Sysmex CA7000 analyzer. ResultsThe multivariate linear regression analysis showed that age, body surface area, and coagulation factor activity had no significant effect on warfarin dosage. While the gene polymor-phisms of CYP2C9 and VKORC1, warfarin concentration, and age had significant contributions to the overall variability in warfarin dose with decisive coefficients at 1.2%, 26.5%, 43.4%, and 5.0% respectively. The final equation was:Y=1.963-0.986× (CYP2C9* 3) +0.893× (VKORC1-1639) +0.002× (warfarin concentration)-0.019× (age). ConclusionMultiple regression equation including gene polymorphisms of CYP2C9 and VKORC1, non-genetic factors of coagulation factor activity, warfarin concentration, age, and body surface area can predict reasonable dosage of warfarin for anticoagulation to achieve individualized management of anticoagulation monitoring and reduce the anticoagulation complications.
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 effects of antiepileptic drugs (AEDs) with warfarin functions and blood coagulation system, to provide the reference for clinicians of the selection of AEDs under the combination therapy with warfarin. Methods Analyse the clinical data of the patient with symptomatic epilepsy from the Second Clinical Medical College of Guiyang University of Chinese Medicine on April 1, 2017, whom taking AEDs and warfarin at the same time, clear the drug adverse reactions, and analysed related literature. Results After the treatment with valproate, abnormal blood coagulation, a danger and emergency data appeared, so we stopped using warfarin immediately, and reduce the dosage of valproate gradually, insteadly, we used levetiracetam as antiepileptic therapy. Monitoring blood coagulation function, when it returned to normal, restart warfarin anticoagulant therapy. Conclusions When start antiepileptic treatment in relevant basic diseases of symptomatic epilepsy, for a variety of combination reactions, AEDs can affect the anticoagulant effect of warfarin, so we need to consider the interaction between drugs and avoid adverse reactions.