Is INR between 2.0 and 3.0 the optimal level for Chinese patients on warfarin therapy for moderate-intensity anticoagulation?

AIM: To examine the optimal range of International Normalized Ratio (INR) for Chinese patients receiving warfarin for moderate-intensity anticoagulation. METHODS: This was a retrospective cohort study conducted at the ambulatory setting of a 1400-bed public teaching hospital in Hong Kong. The INR measurements and occurrence of serious or life-threatening haemorrhagic and thromboembolic events among patients newly started on warfarin from 1 January 1999 to 30 June 2001 for indications with target INR 2-3 were analysed. The INR-specific incidence of bleeding and thromboembolism were calculated. RESULTS: A total of 491 patients were included, contributing to 453 patient-years of observation period. Forty-seven of the 491 patients experienced 25 haemorrhagic events (5.5 per 100 patient-years) and 27 thromboembolic events (6.0 per 100 patient-years). The percentage of patient-time spent within therapeutic INR range (2-3), INR <2 and INR >3 were 50, 44 and 6%, respectively. The incidence of either haemorrhagic or thromboembolic events was lowest (< or =4 events per 100 patient-years) at INR values between 1.8 and 2.4. CONCLUSIONS: An INR of 1.8-2.4 appeared to be associated with the lowest incidence rate of major bleeding or thromboembolic events in a cohort of Hong Kong Chinese patients receiving warfarin therapy for moderate-intensity anticoagulation.     

Evaluation of the clinical and economic impact of a brand name-to-generic warfarin sodium conversion program

BACKGROUND: Substitution of generic warfarin initially was discouraged because of concerns regarding therapeutic failure or toxicity. Although subsequent research with AB-rated (i.e., bioequivalent) warfarin did not confirm initial concerns, the issue is not settled for all clinicians. OBJECTIVES: We sought to provide additional information regarding the clinical and economic impact of warfarin conversion by analyzing a real-life sample of patients receiving long-term anticoagulation therapy who were switched from brand name to generic warfarin. METHODS: Patients who had been taking warfarin for at least 180 days and had received uninterrupted oral anticoagulation 90 days before and 90 days after switching to generic warfarin were included. The switch date was based on the first time generic warfarin was dispensed from our pharmacies. The primary end point was the calculated amount of time each patient's international normalized ratio (INR) values were within the patient-specific target INR range in the 90 days before and after the switch. Data regarding adverse events and medical resource utilization were also collected. Pharmacoeconomic analyses were performed. RESULTS: The analysis included 2299 patients. The overall difference in calculated time INR values were below (22.6% before vs 26.1% after switch, p<0.0001) and within (65.9% before vs 63.3% after switch, p=0.0002) the therapeutic INR range was statistically but not clinically significant. Only 28.0% of patients experienced a change in therapeutic INR control of 10% or less, 33.1% experienced INR control that improved by greater than 10%, and 38.9% experienced INR control that worsened by more than 10%. The difference in total treatment costs associated with brand name and generic warfarin was 3128 dollars/100 patient-years in favor of the generic product. Sensitivity analyses revealed that cost savings associated with warfarin conversion in this health care system were highly dependent on the difference between warfarin costs and cost of treating anticoagulation-related adverse events. CONCLUSIONS: Most of these patients were successfully switched from brand name to generic warfarin. However, supplemental INR monitoring is warranted when one warfarin product is substituted for another to allow timely detection of those patients who experience significant changes in anticoagulation response.     

心脏机械瓣膜置换术后华法林低强度抗凝疗效观察

目的探讨安徽地区汉族人心脏机械瓣膜置换术后华法林低强度抗凝应用于患者的安全性,为瓣膜置换术后患者给予最佳的华法林抗凝剂量及最佳的INR控制标准提供参考。方法对安徽医科大学第一附属医院2010年1月至2013年1月期间509例安徽省地区汉族人群人工机械瓣膜置换术后的患者给予华法林低强度抗凝治疗。随访期间,记录其PT、INR值及华法林剂量。统计出血及血栓、栓塞等不良事件的发生。结果失访及数据不完整的有40例,数据较完整的有469例,随访1～37个月,平均（18.13±6.02）月,总随访1 960.8人年。男211例,女258例,平均年龄（40.52±13.38）岁,其中行MVR 268例,AVR 115例,DVR 86例。所换瓣膜均为双叶机械瓣膜,其中153枚St.Jude Regent瓣膜,291枚CarboMedics瓣膜,111枚国产GKS瓣膜。结果平均INR为2.11±0.56,平均华法林剂量为（3.124±2.4）mg。共有47例抗凝相关并发症,其中出血事件37例（发生率为1.89%pt-y）,血栓、栓塞事件有10例（发生率为0.51%pt-y）。另外,5例死亡,与抗凝相关有3例。术前患者共有316例合并房颤,43例合并左房血栓。结论安徽省人群瓣膜置换术后患者INR控制在1.8～2.2是合适的,可以有效控制血栓、栓塞及出血等并发症的发生。合并房颤患者及行DVR的患者的抗凝相关并发症发生率较高,此类患者应加大复查频次,及时调整华法林剂量。     

Anticoagulation-related outcomes in patients receiving warfarin after starting levofloxacin or gatifloxacin

STUDY OBJECTIVE: To compare anticoagulation-related outcomes in patients receiving stable dosages of warfarin who started levofloxacin or gatifloxacin therapy. DESIGN: Retrospective medical record review. SETTING: Veterans Affairs medical center. PATIENTS: Of 92 patients receiving the same dosages of warfarin for at least 4 weeks before starting antibiotic therapy, 54 received levofloxacin between January and September 2003, and 38 received gatifloxacin between January and September 2004. MEASUREMENTS AND MAIN RESULTS: Data were obtained through the hospital's pharmacy, laboratory, and general patient databases and through electronic medical records. The INRs evaluated were prefluoroquinolone use, defined as the last INR measured before the start of antibiotic therapy (up to 4 wks earlier), and postfluoroquinolone use, defined as any INR measured during antibiotic therapy through 1 week after discontinuation of the antibiotic. Analyzed outcomes included the percentage of patients with postfluoroquinolone INRs that were above 4, that exceeded the therapeutic goal, or that exceeded the goal by more than 1 point; INR changes of more than 0.5, 1, or 1.5 points above the INR before fluoroquinolone use; major or minor bleeding events; requirement for vitamin K administration; warfarin dosage reduction or withholding doses; and warfarin-related hospital, emergency, or urgent care admissions or visits. No significant differences were noted in baseline characteristics with regard to age, sex, prefluoroquinolone INR, or anticoagulation indications between the two groups. The percentage of patients with a postfluoroquinolone INR above 4 was 2% (1 of 54 patients) in the levofloxacin group versus 21% (8 of 38 patients) in the gatifloxacin group (p=0.003). The percentage of patients receiving vitamin K in the levofloxacin and gatifloxacin groups was 0% (0 of 54 patients) and 11% (4 of 38, p=0.026), respectively. For the other anticoagulation-related outcomes, no significant differences were noted between the groups. CONCLUSION: Patients receiving warfarin who take gatifloxacin may be at higher risk for an INR above 4 compared with those taking levofloxacin. Close monitoring of warfarin therapy while concomitantly receiving gatifloxacin is warranted.     

Effect of age on international normalized ratio at the time of major bleeding in patients treated with warfarin

STUDY OBJECTIVES: Because the risk of major bleeding associated with warfarin increases with increasing international normalized ratio (INR) as well as with advanced age, we evaluated the association between age and INR in patients with major bleeding events related to anticoagulation with warfarin. DESIGN: Retrospective record review. SETTING: Two university-affiliated anticoagulation clinics. PATIENTS: Sixty-six patients (mean age 61.2 yrs, range 21-90 yrs) receiving warfarin therapy who experienced major bleeding, defined as bleeding requiring hospitalization, during a 20-month index period. MEASUREMENTS AND MAIN RESULTS: In patients aged 65 years or older, the mean INR at the time of a major bleeding event was significantly lower than that in patients younger than 65 years (INR 3.1 vs 4.2, respectively; p=0.01). For every 1-year increase in age, mean INR at the time of a major bleeding event decreased by 0.03 (p=0.02). CONCLUSION: Patients aged 65 years or older experience warfarin-related major bleeding events at a mean INR 1.1 units lower (95% confidence interval -1.9 to -0.27) than patients younger than 65 years. Older patients may require more aggressive management of overanticoagulation to minimize the risk of major bleeding.     

Randomized, placebo-controlled trial of oral phytonadione for excessive anticoagulation

STUDY OBJECTIVE: To compare the efficacy of managing excessive anticoagulation in the absence of bleeding by either omitting warfarin therapy alone or administering oral phytonadione in addition to omitting warfarin therapy. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Clinical pharmacy anticoagulation service in a group model health maintenance organization. SUBJECTS: Thirty nonbleeding patients with international normalized ratios (INRs) ranging from 6.0-10.0. INTERVENTIONS: Patients were randomized to receive either a single oral dose of phytonadione 2.5 mg or placebo. Both groups omitted warfarin doses until the INR became less than or equal to 4.0. MEASUREMENTS AND RESULTS: The mean calculated time to reach an INR of 4.0 was significantly greater in the placebo than the phytonadione group (2.6 vs 1.4 days, p=0.006). Overcorrection of anticoagulation was significantly more common in patients receiving phytonadione. Overt warfarin resistance was not observed in either group after reinitiating warfarin therapy. No major bleeding or thromboembolic complications occurred, and minor bleeding episodes were similar in both groups. CONCLUSION: The addition of oral phytonadione 2.5 mg reduced the time to achieve an INR of 4.0 by approximately 1 day compared with omitting warfarin therapy alone. Adverse events did not differ between the two groups. Both strategies were effective in managing asymptomatic patients with INRs of 6.0-10.0. Oral phytonadione may be most appropriate for patients at high risk for bleeding in whom the benefit of prompt INR reduction would outweigh the thromboembolic risk associated with INR overcorrection.     

A pilot study of home treatment of deep vein thrombosis with subcutaneous once-daily enoxaparin plus warfarin

OBJECTIVE: To evaluate patient satisfaction, effectiveness, and safety of at-home treatment of acute deep vein thrombosis (DVT) with subcutaneous enoxaparin dosed at 1.5 mg/kg once daily plus oral warfarin. METHODS: Patients with acute DVT and no more than 1 previous episode of DVT received enoxaparin plus oral warfarin until their international normalized ratio (INR) was >2 on 2 consecutive days. Patients were recruited between November 2000 and June 2003, and a home-care nurse visited the patient daily to administer the enoxaparin and to perform a fingerstick INR test. Patients received warfarin at doses adjusted to maintain an INR in the range of 2 to 3. Efficacy and safety were assessed daily by a home-care nurse and then by telephone interview conducted by a pharmacist at 14, 30, and 90 days during follow-up. Patient satisfaction with treatment was assessed by a verbal questionnaire. RESULTS: There were 52 patients enrolled. The mean duration of enoxaparin home treatment was 4.5 days, and the mean INR on discontinuation of enoxaparin was 2.73. Most patients (84.6%) had INRs within the desired therapeutic range (INR value 2-3); no patient had a subtherapeutic INR. There were no symptoms of recurrent venous thromboembolism reported. Major bleeding occurred 7 days after discontinuation of enoxaparin in one patient with impending surgery for removal of a uterine tumor. There were 2 cases of minor bleeding. The patient satisfaction questionnaire revealed that patients considered home treatment to be acceptable. The average cost savings was $2,925 per patient compared with typical inpatient treatment with unfractionated heparin. CONCLUSION: The results of this pilot study suggest that home treatment with initial once-daily enoxaparin in conjunction with long-term oral warfarin is a safe and effective alternative to inpatient therapy with once-daily enoxaparin or unfractionated heparin for select patients with acute DVT. Cost savings are derived from the substitution of inpatient care with home care.     

慢性房颤华法令抗凝治疗的理想INR值探讨

目的:探讨慢性房颤华法令抗凝治疗的理想国际标准化比值(INR)。方法:对115例有血栓栓塞高危因素的慢性房颤患者给予华法令抗凝治疗,定期随访INR,同时观察治疗中发生的血栓栓塞和出血事件。结果:115例患者中有8例共10次发生血栓栓塞事件,7例7次发生与抗凝有关的出血事件,10次血栓栓塞事件中9次发生在INR<1.7,而所有的出血事件都发生在INR>3.5,INR 1.7～3.5时栓塞或出血发生率均较低。结论:INR 1.7～3.5是慢性房颤华法令抗凝治疗较理想的抗凝强度。     

Patient Self-Monitoring of Oral Anticoagulant Therapy

Coumarin derivatives are widely used oral anticoagulants for patients with chronic atrial fibrillation, venous thromboembolism, valvular heart disease, myocardial infarction or a mechanical prosthetic heart valve. Because of the narrow therapeutic window associated with coumarins and the potential for drug interactions, frequent monitoring of anticoagulation is required to maintain the International Normalized Ratio (INR) between 2.0 to 3.5 for most clinical indications. Monitoring of oral anticoagulant therapy is placing a considerable burden on healthcare providers because many patients require life-long treatment with coumarins, and because of an increasing number of elderly patients with conditions that are treated with coumarins. A novel approach that might, in part, address this healthcare need is patient self-monitoring of anticoagulation with a portable coagulometer. Several cohort studies and randomized controlled trials have found that anticoagulation self-monitoring is as good as, or better than, conventional monitoring in a specialized anticoagulation clinic or by a general practitioner. The advantages of anticoagulation self-monitoring include reduced patient inconvenience relating to anticoagulation clinic visits and laboratory monitoring of warfarin therapy, and fewer INR levels outside the therapeutic INR range if INR measurements are preformed more frequently with anticoagulation self-monitoring. Thus, anticoagulation self-monitoring has the potential to reduce the incidence of thromboembolic and bleeding episodes in patients who are receiving long term oral anticoagulant therapy. The potential drawbacks of anticoagulation self-monitoring include the costs of the portable coagulometer. Additionally, self-monitoring is limited to patients who have the cognitive and physical capabilities to perform the technique required for the portable coagulometer.     

306例瓣膜置换术后患者华法林抗凝护理

目的 总结风湿性心脏瓣膜病瓣膜置换术后华法林抗凝治疗的监测与护理要点.方法 以我院心胸外科306例瓣膜置换术后口服华法林患者为研究对象,对其进行护理干预,监测凝血酶原时间（PT）及其国际标准化比率（INR）,观察治疗效果、不良反应.结果 经过规范的抗凝治疗和护理,92.8％的患者的INR控制在适宜范围内,住院期间仅有4％的患者发生因抗凝治疗导致出血或血栓形成及栓塞等并发症.结论 华法林治疗窗窄,剂量个体差异大,抗凝不足可导致血栓,抗凝过量则有出血甚至致死的风险.加强对口服华法林患者的护理干预及健康教育,可以提高患者用药的依从性,达到既有效抗凝,又不产生明显并发症的目的.     

不同抗凝强度华法林治疗非瓣膜性房颤的安全性及缺血性脑卒中发生的危险因素评估

目的 评估华法林不同抗凝强度治疗非瓣膜性房颤的安全性,以及缺血性脑卒中发生的危险因素。方法 纳入2012年1月—2013年12月收治的130例非瓣膜性房颤患者,根据华法林抗凝治疗的强度分为中强度组：华法林中等强度抗凝治疗,国际标准化比率(international normalized ratio,INR)控制在2.0＜INR≤3.0;低强度组：华法林低等强度抗凝,INR控制在1.6≤INR≤2.0,记录2组患者治疗和随访期间缺血性脑卒中、出血栓塞等不良反应的发生率,ROC曲线法分析INR诊断抗凝出血风险,多因素Logistic回归分析患者缺血性脑卒中的危险因素。结果 中强度组缺血性脑卒中、短暂性脑缺血发作和外周动脉栓塞发生率分别为6.70%,3.45%和1.72%,与低强度组的8.33%,4.17%和4.17%比较,无统计学差异(P>0.05);中强度组华法林用量(3.13±0.45)mg·d^-1,INR值2.61±0.32,出血发生率为24.14%;低强度组华法林用量(2.63±0.32)mg·d^-1,INR值 1.84±0.30,出血发生率为9.72%。采用INR诊断患者出血风险,ROC曲线下面积为0.858(95%CI：0.791~0.924),INR的cut-off值2.85,该值下判断出血敏感性为81.1%,特异性为67.2%;多因素logistic回归分析发现年龄、合并高血压、糖尿病、心力衰竭、脑卒中病史、INR、治疗窗内时间、卒中危险评分是非瓣膜性房颤患者缺血性脑卒中发生的独立危险因素(P<0.05)。结论 中、低强度华法林抗凝治疗均有较好的抗凝效果,非瓣膜性心房颤动患者伴有血栓栓塞危险因素应尽早应用华法林抗凝治疗,严密监测INR,INR值控制在1.6≤INR≤2.0,降低和避免出血并发症。     

Leflunomide and warfarin interaction: case report and review of the literature

A 61-year-old Caucasian woman receiving long-term anticoagulation with warfarin for recurrent thromboembolism and atrial fibrillation was found to have an elevated international normalized ratio (INR) after she started leflunomide therapy for rheumatoid arthritis. Her INR had been stable for 4 months before this event. The patient required an overall decrease of 22% in her weekly warfarin dose to maintain a therapeutic INR within the goal range of 2.0-3.0 after adding leflunomide therapy. A comprehensive PubMed/MEDLINE search was conducted to identify literature addressing the potential interaction between warfarin and leflunomide. Evidence describing the interaction and its potential mechanism was limited to one published case report and to in vitro data, respectively. Our case report provides additional support that such an interaction exists and that it was at least partly responsible for the subsequent increase in the patient's INR. Therefore, continued evaluation and documentation of this potential drug interaction is imperative. To reduce the risk of adverse effects related to excessive anticoagulation with the start of leflunomide in patients taking warfarin, clinicians should increase their frequency of INR monitoring and adjust the warfarin dosage accordingly to maintain therapeutic anticoagulation.     

Adequacy of anticoagulation in patients with atrial fibrillation coming to a hospital

STUDY OBJECTIVE: To evaluate the adequacy of anticoagulation in patients with atrial fibrillation (AF) coming to a hospital. DESIGN: Retrospective medical record review. SETTING: Tertiary care hospital. PATIENTS: Consecutive patients with a history of AF who had been prescribed warfarin and who had the international normalized ratio (INR) measured when they arrived at the hospital. Those who developed AF as a complication during hospitalization were excluded. MEASUREMENTS AND MAIN RESULTS: Of 1085 patients, 375 (mean age 73 yrs, 56.3% men) were eligible for further evaluation. Most had nonvalvular AF; in 44.5% the INR was subtherapeutic, in 36.5% it was therapeutic, and in 18.9% it was supratherapeutic. Patients admitted for any thromboembolic event and for ischemic stroke were significantly more likely to have subtherapeutic INRs. CONCLUSION: It is well documented in the literature that warfarin is underprescribed, but our results suggest that even in treated patients, about half are inadequately protected from thromboembolism.     

Quality of anticoagulation care in patients discharged from a pharmacist-managed anticoagulation clinic after stabilization of warfarin therapy

STUDY OBJECTIVE: To determine if transitioning patients from a pharmacist- managed anticoagulation clinic after stabilization of warfarin therapy to physician-managed care alters the quality of anticoagulation care. DESIGN: Retrospective medical record review. SETTING: Pharmacist-managed, urban academic medical center-based outpatient anticoagulation clinic. PATIENTS: Forty patients who were stabilized on warfarin therapy. MEASUREMENTS AND MAIN RESULTS: Quality of anticoagulation care was measured by percentage of international normalized ratios (INRs) in target range, anticoagulation-related health care visits, and responses to satisfaction surveys. A significant decrease in anticoagulation control was observed on transition to physician-managed care. Before transition, 76% of all INRs were in target range versus 48% after transition (p<0.0001, chi(2) test). When performing paired analysis, a median 75% of each patient's INRs were therapeutic before transition compared with 36.5% after (p<0.0001, Wilcoxon signed rank test). Thirty-two percent of first INR values measured after transition from the clinic were in target range, and the median time to first follow-up INR was 41 days. The number of INR values above 4.5 and below 1.5 increased significantly after transition from the anticoagulation clinic (p<0.0001 and p=0.01, respectively, chi(2) test). Before transition from the anticoagulation clinic, two anticoagulation-related emergency department visits were reported in one patient. After transition, 13 cases of additional medical care were reported among seven patients; seven of the 13 cases required an office visit with the physician, and six resulted in emergency room evaluation. None of these cases resulted in hospitalization. Patient satisfaction with clinical care provided by the anticoagulation clinic was significantly higher before transition. CONCLUSION: Transition of patients from a pharmacist-managed anticoagulation clinic back to physician-managed anticoagulation care after stabilization of warfarin therapy was associated with a significant decrease in INR control, increased medical care related to anticoagulation, and decreased patient satisfaction.     

The Use of Vitamin K in Patients on Anticoagulant Therapy

Anticoagulation with antivitamin K (AVK) is very effective for primary and secondary prevention of thromboembolic events. However, questions persist about the risks and management of over-anticoagulation. For reversal of excessive anticoagulation by warfarin, AVK withdrawal, oral or parenteral vitamin K administration, prothrombin complex or fresh frozen plasma may be used, depending on the excess of anticoagulation, the existence and site of active bleeding, patient characteristics and the indication for AVK. In over-anticoagulated patients, vitamin K aims at rapid lowering of the international normalized ratio (INR) into a safe range to reduce the risk of major bleeding and therefore improving patient outcome without exposing the patient to the risk of thromboembolism due to overcorrection, resistance to AVK, or an allergic reaction to the medication. The risk of bleeding increases dramatically when the INR exceeds 4.0–6.0, although the absolute risk of bleeding remains fairly low, <5.5 per 1000 per day. Patient characteristics, including advanced age, treated hypertension, history of stroke, and concomitant use of various drugs, affect the risk of bleeding. The absolute risk of thromboembolism associated with overcorrection appears to be in the same range as the risk of bleeding due to over-anticoagulation. The use of vitamin K in patients with warfarin over-anticoagulation lowers excessively elevated INR faster than withholding warfarin alone; however, it has not been clearly demonstrated that vitamin K treatment does, in fact, lower the risk of major hemorrhage. As vitamin K administration via the intravenous route may be complicated by anaphylactoid reactions, and via the subcutaneous route by cutaneous reactions, oral administration is preferred. A dose of 1–2.5mg of oral phytomenadione (vitamin K₁), reduces the range of INR from 5.0–9.0 to 2.0–5.0 within 24–48 hours, and for an INR >10.0, a dose of 5mg may be more appropriate. Overcorrection of the INR or resistance to warfarin is unlikely if the above doses of vitamin K are used. Vitamin K is less effective for over-anticoagulation after treatment with acenocoumarol or phenprocoumon than after treatment with warfarin.     

机械心脏瓣膜置换术后华法林抗凝治疗的药学监护

目的：探讨药学监护对心脏瓣膜置换术后应用华法林抗凝治疗患者生存质量的影响。方法：对48例接受华法林抗凝治疗的心脏瓣膜置换术患者进行用药教育、监测凝血酶原国际标准化比值、监测出血等不良反应。结果：患者在教育培训前、后抗凝知识评分分别为（4．78±0．52）和（10．23±0．41）分,自我管理能力评分分别为（4．15±1．25）和（10．55±0．20）分（P〈0．05）,出血事件13例,年龄、肝硬化与出血事件显著相关（P=0．046和P=0．016）;血栓栓塞事件2例。结论：对使用华法林抗凝治疗患者进行药学监护能提高使用华法林的依从性,降低出血等并发症发生率。     

心脏机械瓣膜置换术后华法林抗凝观察

目的:探讨心脏机械瓣膜置换术后华法林抗凝治疗的影响因素、给药方法和国际标准比值(INR)的关系。方法:对123例行心脏机械瓣膜置换术后患者进行随访研究。术后使用华法林抗凝,出院后定期复查随访。记录年龄、性别、华法林剂量和INR值等,观察出血、栓塞、死亡等不良事件发生情况。结果:术后无死亡病例,出院发生股静脉血栓1例,牙龈出血11例,泌尿系出血3例。出院随访因抗凝出现不良事件的发生率与国外文献报道相近。结论:心脏机械瓣膜置换术后5d根据INR给予个体化剂量,控制INR值在1.5～2.0之间可以达到一定的抗凝效果,且相对安全。     

华法林致机体出血30例临床特点分析

目的探讨口服华法林药物所致机体出血患者临床特点,并评估重新应用华法林后再出血的危险。方法记录30例服用华法林患者出血时INR范围、出血部位,逆转华法林作用的方式及治疗强度,服华法林后再次出血及死亡的原因。结果 2例因脑疝死亡,28例治愈,其中1例发生右侧腘动脉血栓伴侧枝循环形成,1例2年内反复出现3次上消化出血并1次失血性休克。结论华法林致机体出血好发于服药开始3个月及1年以上者,多因患者未定时监测INR,提示调整治疗强度的INR对减少出血发生率的必要性,强调抗凝宣教及加强随访的重要性。此外,停用华法林血栓栓塞的危险度低,但恢复华法令治疗少数可有复发出血。     

Striking a balance between the risks and benefits of anticoagulation bridge therapy in patients with atrial fibrillation: clinical updates and remaining controversies

Long-term anticoagulation with a vitamin K antagonist (VKA) or the new agent dabigatran is recommended to decrease stroke risk in patients with atrial fibrillation. When patients with atrial fibrillation undergo initiation or interruption of VKA therapy, or experience an isolated subtherapeutic international normalized ratio (INR), bridge therapy with a parenteral anticoagulant may be considered. To describe the literature for anticoagulation bridge therapy in patients with atrial fibrillation, we conducted a MEDLINE search (1966-February 2011) of the English-language literature to identify related studies. Ongoing clinical trials were identified through a search of the ClinicalTrials.gov registry. Major national and international guidelines were gathered and evaluated. Additional literature was obtained through review of relevant references of the identified articles. Bridging is not supported by guidelines or clinical trials for patients starting VKA therapy for atrial fibrillation. A subtherapeutic INR value during long-term VKA therapy may be associated with increased thromboembolic events, but the benefit of bridging has not been demonstrated. When VKA therapy is interrupted for procedures, retrospective and cohort data suggest that the decision to bridge should be based on a patient's thromboembolic and bleeding risks associated with the procedure. Typically, it is recommended to use bridge therapy in patients with atrial fibrillation at high risk for thromboembolism, but the benefit of bridging is less clear in patients at low risk. Not all procedures necessitate anticoagulation interruption. Recent trials suggest that VKAs can be continued when patients are undergoing cardiac device procedures and some types of radiofrequency ablation. Several clinical trials are ongoing that will provide more definitive guidance for perioperative anticoagulation management of patients with atrial fibrillation. Patients taking dabigatran are unlikely to require bridge therapy because of a predictable anticoagulant effect and rapid onset of action. However, evidence for optimal perioperative management of dabigatran is needed.