目的:探讨不同抗凝强度华法林应用于非瓣膜性心房颤动患者的可行性及安全性。方法:91例非瓣膜性心房颤动患者随机分为三组:低抗凝强度［国际标准化比率（INR）1.5～1.9］；标准抗凝强度组（INR 2.0～2.5）和阿司匹林组，观察三组血栓栓塞并发症和出血等不良反应的发生率以及C反应蛋白浓度变化。结果:标准抗凝强度组血栓发生率低于低抗凝强度组、阿司匹林组，不同强度华法林抗凝组血栓栓塞率比较差异无统计学意义；标准抗凝强度组出血发生率低于其他两个组，但三组患者出血发生率比较无统计学意义（Pgt;0.05）；治疗后低抗凝强度组、标准抗凝强度组C反应蛋白浓度明显低于治疗前（Plt;0.05），治疗后阿司匹林组C反应蛋白水平明显高于低抗凝强度组、标准抗凝强度组（Plt;0.01）。结论:华法林抗凝维持INR值在2.0～2.5时能降低非瓣膜性房颤患者血栓栓塞发生率，出血发生率低，有效性和安全性好。
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。
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.
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 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.
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.
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 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.