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.
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。
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。
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 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.
Objective To explore the efficacy and safety of different Wafarin anticoagulation intensities in preventing thromboembolism in patients with paroxysmal non-valvular atrial fibrillation (PAF). Methods The patients with PAF were enrolled and divided into four groups. The patients were treated by different Wafarin anticoagulation intensities. The values of the control of international normalized ratio (INR) were 1.3-1.6 in Group 1, 1.7-2.0 in Group 2, 2.0-2.5 in Group 3, and 2.6-3.0 in Group 4. Main destination events, secondary destination events, main bleeding events, secondary bleeding events, main events (main destination events + main bleeding events), secondary events (secondary destination events + secondary bleeding events), and total events (main events + secondary events) were observed and compared in the four groups, respectively. Relevance between events of thromboembolism as well as bleeding and INR was analyzed. Results A total of 868 patients with moderate-high risk PAF were enrolled, and 826 patients (167 cases in Group 1, 220 cases in Group 2, 215 cases in Group 3, and 224 in Group 4) were included in final analysis. The follow-up results showed that the increase of INR led to a reduction in the destination events (there were significant differences between Group 1 and Group 2, 3, and 4 with Plt;0.05), but the bleeding events tended to rise. In terms of the incidence of main events, secondary events and total events, Group 1 was higher than Group 2, 3, and 4 with significant differences (Plt;0.05), except that the main event incidence of Group 1 was not significantly different from that of Group 4 (Pgt;0.05). Conclusion For Chinese patients with PAF, anticoagulation intensities of Wafarin with INR 1.7-2.5 can reduce the destination events with no rise in bleeding events. The anticoagulation intensities within this extent are safe and effective
ObjectiveTo investigate the influence of high activity of CYP2C9 (Cytochrome P450 proteins 2C9)and VKORC (Vitamin K epoxide reductase C)on warfarin anticoagulation of patients after heart valve replacement (HVR). MethodsFrom February 2010 to May 2013, 40 patients with high activity of CYP2C9 and VKORC underwent HVR in the Department of Cardiac Surgery, the First Affiliated Hospital of Zhengzhou University. There were 18 male and 22 female patients with their age of 40-51 (45.18±2.93)years. There were18 patients receiving mitral valve replacement (MVR), 14 patients receiving MVR and tricuspid valvuloplasty (TVP), and 8 patients receiving double valve replacement (DVR). Depen-ding on whether they received preoperative genetic polymorphism detection of CYP2C9 and VKORC1, all the patients were divided into 2 groups with 20 patients in each group. Patients in group A didn't receive preoperative genetic polymorphism detection of CYP2C9 and VKORC1, while patients in group B received preoperative genetic polymorphism detection of CYP2C9 and VKORC1. Postoperatively, periodic examination of international normalized ratio (INR)was performed to adjust warfarin dosage. Time to reach expected INR value and morbidity were collected. All the patients were followed up for 3-12 months after discharge. Monthly telephone follow-up was performed to record INR values, morbidity and general recovery. ResultsPostoperatively, in group A, 2 patients had cerebral infarction, 2 patients had popliteal artery throm-bosis, 1 patient had pulmonary embolism, and 1 patient had thrombosis in the annulus. Expected INR was achieved 15-20 days after warfarin treatment among the other 14 patients without thromboembolism. Three months after surgery, CYP2C9 and VKORC1 gene polymorphism was examined to find 17 patients with positive CYP2C9*1/*1 (*2CC/*3AA)and positive VKORC1-1639 GA, and 3 patients with positive CYP2C9*1/*1 (*2CC/*3AA)and positive VKORC1-1639 GG. In Group B, patients received aspirin (100 mg/d)and low molecular heparin (0.4 ml/d)in addition to warfarin since the second posto-perative day. Expected INR was achieved 5-9 days after warfarin treatment, and then aspirin and low molecular heparin were discontinued. During the 6 months follow-up period, no obvious thromboembolism was found, and only 1 patient had epistaxis who was cured with nasal tamponade. ConclusionPreoperative detection of genetic polymorphisms of CYP2C9 and VKORC1 can provide important guidance for warfarin anticoagulation after HVR.
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.