Objective Influence factors of the stable warfarin dose in the early period after mechanical prosthetic valve replacement were analyzed to guide the anticoagulation therapy for these patients. Methods A total of 288 patients within 6 months after mechanical prosthetic valve replacement in West China Hospital were followed up and registered at outpatient department from July 2012 to April 2014, including basic information (name, sex, age, height, weight, etc.), general clinical data (cardiac function, heart rate, surgery pattern, etc.) and related data about anticoagulation therapy. The target international standardized ratio (INR) range was 1.60 to 2.20 and the acceptable INR was 1.50 to 2.30. The sex, age, height, body weight, body mass index (BMI), body surface area (BSA) and related clinical factors were analyzed to find the relationship with the dose of warfarin. Results Sex was found to have a significant effect on the stable warfarin dose (P<0.05). Women needed a lower stable warfarin dose than men during the early anticoagulation therapy. There was no significant difference in the stable warfarin dose of patients with different ages, rhythms, NYHA classification, surgery pattern and diseases before operation; but the stable warfarin dose was lower in the patients with radiofrequency ablation during valve replacement procedures than the patients with single valve replacement (P<0.05). There was an association between age, height, weight, BMI, BSA and the stable warfarin dose withR2 of 1.2%, 3.2%, 3.5%, 1.1%, 4.2%, respectively and they could explain 6.1% of variability in warfarin dose. Conclusion During early anticoagulation therapy in patients with mechanical prosthetic valve replacement, it is necessary to consider the effects of various preoperative factors, drug factors and demographic factors on warfarin dose. Even though there is an association between age, height, weight, BMI, BSA and the stable warfarin dose, which can only explain 6.1% of variability in warfarin dose, thus cannot guide the postoperative anticoagulation of these 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.
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 evaluate the quality of warfarin anticoagulant therapy in patients with stable stage after mechanical valve replacement surgery, to observe the effect of compound salvia miltiorrhiza tablet on the anticoagulant effect of warfarin in patients after mechanical valve replacement, and to understand the impact of genetic polymorphisms of VKORC1, CYP2C9 and CYP4F2 on warfarin resistance in patients with mechanical valve replacement in the stable period.MethodsFrom July 2011 to February 2014, 1 831 patients who had ≥ 6 months after mechanical valve replacement surgery were enrolled at the outpatient follow-up. The basic clinical data were recorded. Anticoagulant therapy uses a target international normalized ratio（INR, 1.60–2.20) and a weekly warfarin dose adjustment strategy. Forty-six patients who needed compound salvia miltiorrhiza tablet were screened and the INR values. Before and after taking tablets were recorded and compared. The patients were divided into three groups according to the percentile of warfarin dosage including a warfarin sensitive patients group, a control patients group, and a warfarin resistance patients group. And 101 of them were selected. TIANGEN blood DNA Kit blood genomic DNA extraction kit was used to extract samples and polymerase chain restriction fragment length polymorphism (PCR-RELP) was used to determine the genotypes of patients. The detected gene loci included CYP4F2: rs2108622C>T locus; VKORC1:1639G>A locus; VKORC1:1173C>T locus; CYP2C9*2: rs1799853C>T locus; CYP2C9*3:1061A>C locus.ResultsThe time in therapeutic range (TTR) and fraction of time in therapeutic range (FTTR) in the target INR range of the patients included in the study period was 27.2% and 49.4%, respectively, and the TTR and FTTR in the acceptable INR range was 34.25% and 63.36%, respectively. Before and after the addition of compound salvia miltiorrhiza tablets, the INR value was 1.55±0.03 and 1.69±0.30, respectively, and the difference was statistically different (P<0.05). A total of 101 patients with genetic testing, in which the C/T composition of the VKORC1: 1173C>T locus increased in the warfarin sensitivity, contrast and warfarin resistance patients, while the ratio of allelic loci of C/T in CYP2C9*3: 1061A>C loci decreased in turn. There was no difference in the CYP4F2 gene, VKORC1639 gene, and CYP2C9*2 locus. The IWPC model predicts that warfarin dose is only consistent with the actual warfarin dose in warfarin sensitive patients.ConclusionRelatively low TTR and FTTR are acceptable in patients with stable stage after mechanical valve replacement. It is beneficial to the patients with compound salvia miltiorrhiza tablets in terms of some appropriate patients. VKORC1: 1173C>T site and CYP2C9*3: 1061A>C site mutation is the main pharmacological gene factor of warfarin dose sensitivity and warfarin resistance in stable period after mechanical valve replacement. The IWPC dose prediction model is only consistent with the actual dose of warfarin sensitive patients.
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.
The management of women with mechanical heart valves during pregnancy remains difficult and controversial. The selection of prosthetic heart valve, management during pregnancy and delivery period, guidelines and anticoagulation strategy used in patients with a mechanical heart valve in China are summarized in this review.
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.
目的:心房纤颤是老年最常见的心律失常之一,并且带来了如外周血管血栓形成、肺梗死、脑卒中等并发症。口服抗凝治疗是预防该类并发症的有效手段,但监测繁琐、有药物不良反应风险等。本实验为寻找有效的房颤管理模式,设计了社区管理模式,并与专科管理模式进行对照,以研究社区管理模式是否适合老年房颤患者的管理。方法:纳入在我院就诊的老年房颤患者107名,随机分入社区管理组及专科管理组,其中专科管理组患者在珠海市人民医院门诊常规就诊,而社区管理组在所属社区进行治疗。对照比较在抗凝达标率、华法林相关不良反应事件发生率(出血、血栓事件)、及费用方面的差异。结果:与专科管理组比较,社区管理组在抗凝达标率(分别为612%,642%,Pgt;005)、出血及血栓事件(P值分别为0133,0279)发生率方面无明显统计学差异,但是在总体费用方面存在着统计学差异(Plt;0001)。结论:老年房颤患者华法林抗凝治疗在社区管理有着与专科管理相似的可行性、安全性及有效性,并且有费用方面的优势。
Objective To investigate whether the individualized anticoagulation therapy based on CYP2C9 and VKORC1 gene is superior to empirical anticoagulation therapy after artificial heart valve replacement surgery in Uygur patients. Methods From December 2012 to December 2015, 210 Uygur patients who underwent artificial heart valve replacement surgery at the First Affiliated Hospital of Xinjiang Medical University were randomly assigned to a genetic anticoagulation therapy group (group A, n=106, 41 females and 65 males, aged 44.7±10.02 years) or an empirical anticoagulation therapy group (group B, n=104, 47 females and 57 males, aged 45.62±10.01 years) according to the random number table. CYP2C9 and VKORC1 genotypes were tested in the group A and then wafarin of administration in anticoagulation therapy was recommended. Patients in the group B were treated with conventional anticoagulation. Patients in both groups were followed up for 1 month and coagulation function was regularly tested. Results The percentage of patients with INR values of 1.8-2.5 after 4 weeks warfarin anticoagulation treatment in the group A was higher than that in the group B (47.1% vs. 32.7%, P=0.038). The rate of INR≥3.0 in the warfarin anticoagulation therapy period in the group A was lower than that in the group B (21.6% vs. 26.5%, P=0.411). The time to reach the standard INR value and the time to get maintenance dose were shorter in the group A compared with the group B (8.80±3.07 d vs. 9.26±2.09 d, P=0.031; 14.25±4.55 d vs. 15.33±1.85 d, P=0.032). Bleeding occured in one patient in the group A and three patients in the group B (P=0.293). Embolic events occured in three patients in the group A and five patients in the group B (P=0.436). Conclusion Compared with the empirical anticoagulation, the genetic anticoagulation based on wafarin dosing model can spend less time and make more patients to reach the standard INR value. However there is no significant difference between the two groups in the ratio of INR≥3.0, bleeding and embolic events in the warfarin anticoagulation therapy.
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.