华法林抗凝治疗中出血和血栓栓塞性不良反应及相关因素探讨

目的研究华法林抗凝治疗过程中出血和血栓栓塞性不良反应并识别相关危险因素。方法观察北京大学人民医院2001-04~2003-11抗栓门诊华法林使用大于4周患者的出血和血栓栓塞事件,事件分为小事件、严重事件和威胁生命或致命性事件,应用多种统计方法分析出血和血栓栓塞事件发生情况及相关危险因素。结果128例服用华法林患者,平均年龄67岁(25~83岁),34例(占26·6%)共发生41次出血事件,严重和致命性的血栓栓塞事件5例(占3·9%)。年龄、肝硬化与出血事件显著相关(P=0·040,P=0·014)。结论出血是华法林抗凝治疗最主要的不良反应,而年龄、肝硬化是出血事件的重要危险因素。     

Risks and benefits of azathioprine therapy

The risk of lymphoma may be increased by about fourfold in patients with inflammatory bowel disease treated with thiopurines. The increased risk could be a result of the medications, the severity of the underlying disease, or a combination of the two.     

华法林抗凝治疗中出血和血栓栓塞性不良反应及相关因素探讨

目的 研究华法林抗凝治疗过程中出血和血栓栓塞性不良反应并识别相关危险因素。方法 观察北京大学人民医院2001-04～2003-11抗栓门诊华法林使用大于4周患者的出血和血栓栓塞事件，事件分为小事件、严重事件和威胁生命或致命性事件，应用多种统计方法分析出血和血栓栓塞事件发生情况及相关危险因素。结果 128例服用华法林患者，平均年龄67岁（25—83岁），34例（占26．6％）共发生41次出血事件，严重和致命性的血栓栓塞事件5例（占3．9％）。年龄、肝硬化与出血事件显著相关（P=0．040，P=0．014）。结论 出血是华法林抗凝治疗最主要的不良反应，而年龄、肝硬化是出血事件的重要危险因素。     

Periprocedural management of anticoagulation in patients on extended warfarin therapy

Patients receiving chronic anticoagulation therapy pose a clinical challenge when therapy needs to be interrupted for surgical or invasive procedures. Maintaining anticoagulation places them at risk of serious bleeding complications, whereas discontinuing anticoagulation puts them at risk of thromboembolic complications. The main patient groups that may require a periprocedural alternative to oral anticoagulation include patients with prosthetic heart valves, atrial fibrillation, and hypercoagulable states and those with chronic venous thrombosis undergoing surgery. Currently, there is little consensus on appropriate perioperative management of patients on long-term warfarin therapy. This article is an attempt to bring together all the available data on periprocedural bridging to assess the available options for patients undergoing surgical procedures and to provide a rationale for using low-molecular-weight heparins (LMWHs) while individualizing the risks versus benefits in a given patient population.     

Risks and benefits of adding anti-platelet therapy to warfarin among patients with prosthetic heart valves: a meta-analysis

OBJECTIVES: The objective of this study was to compare the effectiveness and safety of adding dipyridamole or aspirin to warfarin among patients with prosthetic heart valves using meta-analytic techniques. BACKGROUND: Patients with prosthetic heart valves are at increased risk for valve thrombosis and arterial thromboembolism. Oral anticoagulation alone, or the addition of antiplatelet drugs, has been used to minimize this risk. An important issue is the effectiveness and safety of the latter strategy. METHODS: A combined MEDLINE and manual search was made for relevant articles from 1966 to November 1999. Standard meta-analysis techniques were used. RESULTS: Ten studies involving 2,199 subjects met the inclusion criteria. Compared with anticoagulation alone, the addition of an antiplatelet agent reduced the risk of thromboembolic events (odds ratio [OR]: 0.41, p < 0.001) and total mortality (OR: 0.49, p < 0.001). The risk of major bleeding was increased when antiplatelet agents were added (OR: 1.50, p = 0.033). For major bleeding, the comparison of trials performed before and after 1990 (OR: 2.23 and 0.88, respectively) showed that the chi-square test for heterogeneity was significant (p = 0.025). The latter trials used low-dose aspirin, suggesting that the risk of bleeding may be lower with contemporary low-dose (100 mg daily) aspirin. CONCLUSIONS: Adding antiplatelet therapy, especially low-dose aspirin, to warfarin decreases the risk of systemic embolism or death among patients with prosthetic heart valves. The risk of major bleeding is slightly increased with antiplatelet therapy. Nonetheless, the risk of bleeding appears to have diminished with the lower doses of aspirin used in the more recent trials, resulting in a favorable risk-to-benefit profile.     

Gains and losses of warfarin therapy as performed in an anticoagulation clinic

BACKGROUND: Knowledge of the net benefit of warfarin therapy in routine care is needed to define realistic management recommendations, but lack of randomized controls precludes conventional risk-benefit analysis. OBJECTIVE: Assess risk and benefit of routine warfarin therapy in an anticoagulation clinic. DESIGN: Retrospective observational analysis. PATIENTS: A total of 1435 outpatients on warfarin for a total of 1613 patient years, treated to prevent the target events recurrent venous thromboembolism (VTE) or myocardial infarction (MI), and stroke in patients with atrial fibrillation (AF) or mechanical heart valves. MEASUREMENTS: Major bleeding and thromboembolic (TE) events and all deaths. CALCULATIONS: Expected annual target event rates without warfarin were from published data. Differences between combined major events observed with warfarin, and expected without warfarin were calculated. RESULTS: In the total material, annual rates were 3.0% major TE events, 1.1% major bleeding events, 0.12% fatal bleeding, and a benefit/risk ratio of 3.8. The net gain, expressed in reduced combined bleeding and target TE annual event rate, was 9.9% in secondary prophylaxis in AF, 4.4% in VTE patients, 2.7% in post-MI patients, 2.4% in primary prophylaxis in AF and 0.6 in patients with mechanical heart valves. The apparent benefit/risk ratio was 3.9 in VTE patients, 5.8 in AF patients and 1.1 in patients with mechanical heart valves. CONCLUSION: Net effects of prolonged warfarin therapy in patients with VTE and AF performed in an anticoagulation clinic have an acceptable risk/benefit ratio, comparable with what has been obtained in elective clinical trials.     

Pharmacogenetic distribution of warfarin and its clinical significance in Korean patients during initial anticoagulation therapy

During warfarin treatment, determining the optimal dose and maintaining the target PT-INR are challenging. Increasing evidence supports the theory that genotypic polymorphisms influence an individual’s warfarin dose requirement. In this study, we evaluated allele frequencies and effects of CYP2C9 and VKORC1 on warfarin response during initial anticoagulation therapy in Korean patients. We enrolled patients who had initiated warfarin therapy and undergone PT-INR testing at least three times within the first month of anticoagulation therapy. All the participating patients were tested for the detection of CYP2C9*3 (c.1075A>C) and VKORC1-1639G>A. A melting-curve analysis after real-time PCR was performed using CYP2C9*3 and VK1639 genotyping kits (Idaho Technology, US). A total of 37 patients were enrolled in this study. CYP2C9*1/*1 (87%) and VKORC1-1639AA genotypes (89%) were predominant in Korea. The CYP2C9*3 and VKORC1-1639G alleles were found in five (13%) and four patients (11%), respectively. Patients with the CYP2C9*3 allele received a lower warfarin dose (P = 0.018) and tended to show more rapid PT-INR increase than CYP2C9*1/*1 genotype. Patients with the VKORC1-1639G allele nonsignificantly received higher warfarin dose than those without. The CYP2C9*3 and VKORC1-1639G alleles influenced warfarin response during the first month of anticoagulation therapy. Considering these results, CYP2C9 and VKORC1 genotyping can be an useful tool to estimate initial warfarin dose and frequency of PT-INR monitoring during the first month of anticoagulation therapy.     

Long-term anticoagulation for venous thromboembolism: duration of treatment and management of warfarin therapy

Treatment of venous thromboembolism (VTE) should be continued until the reduction of recurrent VTE that anticoagulation is expected to achieve no longer outweighs the increase in bleeding associated with therapy, or until the patient wants to stop treatment even if treatment is expected to be of benefit. Reversibility of risk factors for VTE is the most important factor that influences risk of recurrence and duration of therapy. VTE associated with a reversible risk factor (eg, surgery) is treated for 3 months; unprovoked VTE often benefits from indefinite therapy provided patients do not have risk factors for bleeding; and cancer-associated VTE is usually treated indefinitely. A systematic approach to managing warfarin therapy improves its efficacy, safety, and acceptability.     

心脏瓣膜置换并射频消融术后华法林抗凝治疗的方法探讨

目的探讨心脏瓣膜置换并直视射频消融术后华法林的抗凝治疗方法。方法将130例心脏瓣膜病合并房颤患者分为2组,A组(60例)行瓣膜置换并射频消融术治疗,术后服用胺碘酮治疗6个月,同时服用华法林抗凝治疗;B组(70例)单纯行瓣膜置换术治疗,术后仅服用华法林抗凝治疗。结果术后随访3～16个月,A、B组死亡各1例,均为非抗凝相关死亡。A组出现抗凝所致轻度出血5例、血栓栓塞0例,INR异常升高4例;B组分别为3、3、1例。两组比较,P均>0.05。达抗凝稳态时,两组不同术式患者华法林剂量比较,P均>0.05。达到抗凝稳态时,A组华法林剂量为(2.43±0.58)mg/d,INR为1.83±0.55。结论瓣膜置换同期直视射频消融术后患者应加强抗凝监测,根据INR适度减少华法林用量,避免发生出血。     

老年心脏机械瓣置换术后华法林低强度抗凝疗效观察

目的 探讨老年心脏机械瓣置换术后华法林低强度抗凝标准及安全性。方法 回顾性分析2004年1月~2014年6月在我院心血管外科接受心脏机械瓣置换术后进行低强度抗凝治疗、资料完整患者356例,其中男性203例,女性153例,年龄60~73(64.3±5.1)岁。根据其手术方式分组:主动脉瓣置换术(AVR)组101例、二尖瓣置换术(MVR)组164例、主动脉瓣联合二尖瓣置换术(DVR)组91例。再根据其国际标准化比值(INR)进一步分为低水平组(INR1.6)19例、目标组(1.6≤INR≤2.5)299例、高水平组(INR2.5)38例。连续随访,记录其INR、血栓及出血等不良事件发生率。结果 本组患者发生血栓5例(1.4%),出血49例(13.8%),目标INR 1.6~2.5。AVR组、MVR组和DVR组患者术后出血比例比较无统计学差异,低水平组、目标组和高水平组患者术后出血比例比较有统计学差异。结论 老年人心脏机械瓣置换术后,口服华法林维持INR在1.6~2.5,抗凝效果理想。