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.
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.
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.
ObjectiveTo systematically review therapy-related complications incidences of warfarin with different anticoagulation intensity in Chinese after mechanical heart valve replacement, and to explore the suitable anticoagulation intensity of warfarin.
MethodsWe electronically searched The Cochrane Library (Issue 2, 2013), EMbase, PubMed, CNKI, CBM, WanFang Data and VIP for studies about therapy-related complications rates of warfarin with different anticoagulation intensity in Chinese after mechanical heart valve replacement from inception to March 2013. Two reviewers independently screened literature according to inclusion and exclusion criteria, extracted data, and assessed methodological quality of included studies. Then meta-analysis was performed using RevMan 5.2.
ResultsA total of 7 studies involving 3 787 cases were finally included, 2 985 cases in Group A (targeted INR≤2.3) and 802 cases in Group B (targeted INR > 2.3). The results of meta-analysis showed that, compared with Group B, the total therapy-related complications incidence of warfarin with different anticoagulation intensity significantly decreased in Group A (OR=0.35, 95%CI 0.28 to 0.44, P < 0.000 01). The incidence of hemorrhage in Group A (OR=0.15, 95%CI 0.08 to 0.27, P < 0.000 01) was lower than that in Group B. However, the incidence of embolism in Group A was higher than that in Group B (OR=2.77, 95%CI 1.54 to 4.98, P=0.000 7).
ConclusionApplying low-intensity anticoagulation for Chinese patients after mechanical heart valve replacement could reduce the overall incidences of anticoagulation-related complications and hemorrhage, but it could also significantly increase the incidence of thrombosis.
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.
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 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.
Objective To assess different anticoagulant regimens in pregnant women with mechanical heart valves: taking oral warfarin throughout the pregnancy, or heparin in the 1st trimester and oral warfarin for the other trimesters. The main outcome measures were major maternal complications and perinatal outcomes. Methods The MEDLINE, EMbase, CBM and CNKI were searched. The quality of the included studies was evaluated and data were extracted by two reviewers independently. Meta-analyses were performed on the results of homogeneous studies. Result Seven studies involving 629 pregnancies in 469 patients met the inclusion criteria for this review, all of which were retrospective surveys. The comparison between the administration of heparin in the 1st trimester plus oral warfarin for the other trimesters and warfarin throughout the pregnancy showed that, there are not significant different in the incidence of major maternal complications and the incidence of adverse perinatal outcomes. Conclusion Compared with the administration of warfarin throughout the pregnancy, the administration of heparin in the 1st trimester and oral warfarin for the other trimesters might increase the incidence of major maternal complications, but with a similar incidence of adverse perinatal outcomes.
Abstract: Objective To investigate the anticoagulation effect of warfarin on pregnant women with prosthetic mechanical heart valves during the whole course of pregnancy and their fetuses. Methods Followup survey was carried out on 103 pregnant women with prosthetic mechanical heart valves treated in the Second Xiangya Hospital of Central South University from April 1998 to June 2010. Their age ranged from 19 and 38 years (26.4±3.8 years). All the 103 pregnant women were given oral administration of warfarin during the whole course of pregnancy. The average dose of domestic warfarin was 3.30±0.43 mg/d (87 cases), while the average dose of imported warfarin was 2.90±1.05 mg/d (16 cases). Results None of the patients suffered from serious embolic events. One patient suffered from spontaneous peritoneal hemorrhage. There were 4 cases of intrauterine deaths, and 5 cases of fetal malformation including 1 case of Down’s syndrome and 4 cases of hydrocephalus. Six cases of low birth weight infants and 1 case of ABO hemolytic disease were also found. All the other neonates were healthy with normal weight. No pregnant women suffered from postpartum hemorrhage. Conclusion Oral administration of low dose warfarin (lt;5 mg/d) during the whole course of pregnancy is a relative safe and effective anticoagulation protocol.
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.
