1例胺碘酮致华法林抗凝作用增强病例分析

目的 探讨临床药师在华法林抗凝治疗时联用胺碘酮引起国际标准化值(INR)异常升高的处理方法及药学监护。 方法 通过对照华法林与其他药物相互作用的情况,确定引起INR值异常波动的药物,及时调整华法林剂量,加强凝血功能的监测,并从华法林与胺碘酮的作用机制、相互作用、两药联用后抗凝作用与两药的剂量、浓度相关性等方面阐述胺碘酮对华法林抗凝作用的影响。 结果 INR异常波动为华法林与胺碘酮联用所致,两药联用可增强华法林的抗凝作用,增加出血风险,通过停用华法林3 d,INR恢复到目标值范围,继续给予华法林抗凝治疗,患者情况控制平稳,顺利出院。 结论 临床药师通过对患者有效的药学监护,可协助临床及时发现药物治疗相关问题。在使用与华法林有相互作用的药物时要考虑其对抗凝治疗的影响,一方面要充分了解药物合用时的药理学及药动学变化,另一方面要加强监测,以便及时调整用药方案,提高临床用药的安全性和合理性,更好地为患者提供药学服务。     

1例房颤患者服用华法林抗凝治疗的药学监护

1例86岁男性房颤患者,入院后给予华法林抗凝治疗,期间发现患者国际标准化比值(INR)波动较大。临床药师从疾病及药物相互作用等多方面因素进行分析,同时结合药物代谢动力学和药效学特点,向临床提供合理建议,对患者进行用药指导,保障患者用药安全。     

4例华法林抗凝患者INR异常升高的药学监护

目的:探讨华法林长期抗凝患者引起标准化比值(international normalized ratio,INR)异常升高的影响因素,总结临床药师对该类患者的药学监护和用药教育。方法:临床药师参与了4例使用华法林抗凝治疗患者INR异常升高的救治过程。临床药师对患者的用药史进行了详细分析,协助医师和患者寻找INR异常升高的原因,为患者基因检测服务和结果解读,对华法林长期抗凝患者进行用药教育。结果:4例患者中2例长期使用华法林INR稳定,分别因最近加用中药和病情变化致使INR异常升高;2例在开始加用华法林时INR突然升高,基因检测结果提示患者应该使用更低剂量的华法林治疗。结论:在华法林抗凝治疗的过程中,开始治疗时出现INR异常升高,多为患者基因型影响,应该根据基因型等影响因素调整为更低剂量的华法林;在长期治疗过程中,突然出现INR异常与合并用药有关,去除影响因素可以使INR恢复。患者使用华法林治疗,在加用其他药物过程中,需要谨慎监护。     

1例房颤患者服用华法林期间INR值异常波动的药学监护

1例78岁房颤患者长期服用华法林,1NR值控制在1．6～2．5。入院当日测PT41．6S,INR3．53,遂停用华法林。4d后测INR1．25,低于正常水平,患者重新口服华法林。因关节疼痛加用塞来昔布,监测凝血四项显示PT、INR值分别由14．4S、1．25上升至36．7S、3．12。临床药师分析患者所用药物中,氯雷他定、塞来昔布均可加强华法林的抗凝作用,建议停用华法林、静脉注射维生素K1,医师采纳。此后,继续监测患者的凝血指标,至INR值回落后恢复使用华法林。患者住院期间未发生出血及栓塞事件。     

临床药师参与1例肝功能不全并心房颤动患者华法林抗凝治疗的临床实践

1例70岁肝硬化失代偿期女性患者,入院后给予利尿、保肝、抗感染等对症处理,因心房颤动伴左下肢深静脉血栓给予华法林2.5 mg·d-1抗凝治疗。华法林连续治疗第8天查凝血酶原时间(PT)49.9 s,国际标准化比值(INR)4.19,遂停用华法林。第10天复查PT 40.1 s,INR3.39,继续停用华法林。第12天查PT 28.0 s,INR 2.39,遂恢复华法林1.25 mg·d-1抗凝治疗,并继续监测PT-INR。第15天复查PT 21.7 s,INR 1.87,华法林增量至1.875 mg·d-1。第17天查PT23.9 s,INR 2.05,华法林维持1.875 mg·d-1。     

心房颤动的华法林抗凝治疗存在的临床问题

目的：探讨房颤患者华法林抗凝治疗存在的临床问题。方法：分析2006～2008年新疆塔城地区人民医院内科67例心房颤动患者华法林抗凝治疗的随诊临床资料。结果：10例不能定期门诊随诊监测INR,4例发生出血而停药,2例发生血栓及栓塞,3例出现皮疹及皮肤瘙痒而停药,INR未达标率24．1％。结论：房颤患者华法林抗凝治疗存在依从性差,达标率低,受当地医疗条件限制,部分医师和患者对房颤的危险及华法林抗凝治疗的重要性认识不足等临床问题。     

临床药师参与1例卒中伴房颤患者的抗凝治疗分析

目的探讨临床药师参与卒中伴房颤患者抗凝治疗的方法和药学服务。方法临床药师参与1例卒中伴房颤患者的抗凝诊疗过程,针对抗凝治疗指征及目标值、华法林桥接低分子肝素的目的、华法林的药物相互作用、INR异常升高的处理以及华法林的用药教育等方面进行综合分析。结果临床药师在抗凝治疗中,为患者建立了抗凝治疗信息档案,同时发现抗凝治疗问题,及时向医师提供合理化的治疗建议。结论临床药师参与抗凝治疗管理,促进患者安全、合理、有效地使用药物。     

房颤患者华法林治疗临床探讨

目的探讨华法林在房颤患者抗凝治疗中的使用方法及临床效果,以减少房颤患者脑卒中的发生率,强调需密切监测标准化比值（INR）,以减少华法林的不良反应。方法总结2004年5月至2009年5月使用华法林抗凝治疗的房颤患者60例,进行回顾性分析。结果房颤患者使用华法林抗凝治疗后脑卒中的年发生率为3．33％、无出血并发症的发生。结论无抗凝禁忌证的房颤患者,均应使用华法林抗凝治疗,但应密切监测服用期间国际标准化比率（INR）,确保华法林的安全使用。     

IWPC模型对下肢深静脉血栓形成患者 华法林初始低强度抗凝疗效的影响

目的：评价国际华法林药物基因组学联合会（IWPC）模型对下肢深静脉血栓形成患者（DVT）华法林初始抗凝疗效的影响。方法：100例DVT患者随机分为两组：研究组68例和对照组32例,均给予华法林抗凝治疗。研究组患者采用荧光染色原位杂交分析技术进行CYP2C9和VKORC1基因检测,利用IWPC模型计算华法林初始剂量,并根据国际标准化比值（INR）监测结果调整华法林至合适剂量;对照组直接根据INR监测结果调整华法林至合适剂量。比较两组患者在INR首次达标时间、INR达标维持时间、华法林抗凝治疗3、5、7天INR、INR达标率和INR总达标率、7天华法林累积剂量及治疗范围时间（TTR）的差异。结果：研究组患者CYP2C9 1075A＞C基因以AA型为主（91.18%）,C等位基因突变率5.15%,VKORC1 1639AA型79.41%,G等位基因携带率11.03%。研究组患者INR首次达标时间较对照组明显缩短（P＜0.001）,INR达标维持时间明显增加（P=0.02）,华法林抗凝治疗3天INR及INR达标率明显高于对照组（P=0.01）,且TTR为47.27%,较对照组29.01%明显增加（P＜0.001）。结论：IWPC模型有助于提高下肢深静脉血栓形成患者华法林初始抗凝疗效,但其在华法林长期抗凝中的应用价值有待于临床进一步验证。     

1例华法林抗凝患者INR异常升高病例分析

目的:探讨导致华法林抗凝患者国际标准化比值(INR)异常升高的影响因素,以及临床药师对这类病例的药学监护和处理。方法:临床药师参与1例服用华法林抗凝患者INR异常升高的处理,通过相关基因检测及查阅文献,探讨可能的原因及解决方案,为临床提供合理用药建议。结果:患者的基因型、合用的药物均可能导致INR异常升高,根据患者具体情况设计了个体化给药方案,最终使INR维持在目标范围。结论:临床药师在治疗团队中可发挥专业特长,从多角度全面分析影响华法林抗凝作用的因素,对医生及患者分别开展有针对性的药学服务,保证抗凝治疗的有效性、安全性。     

Effects of prednisone on the International Normalized Ratio.

PURPOSE: The effects of prednisone on the International Normalized Ratio (INR) values of a patient were examined. SUMMARY: A 66-year-old white man with a history of multiple myeloma was treated in an ambulatory care anticoagulation clinic for deep vein thrombosis. His INR values were normal during therapy with warfarin 14 mg weekly and thalidomide 300 mg daily. His INR values began to increase after three months of starting prednisone 10 mg daily. His weekly dose of warfarin was changed over the next two years, and his dietary intake of vitamin K was increased. For every INR value that was below the therapeutic goal, the patient was not taking prednisone; every time the INR value was above the therapeutic goal, he was taking prednisone. In November 2004, the prednisone and thalidomide were stopped and only the warfarin was continued. After a few dosage increases, ending with a weekly warfarin dose of 21 mg, the patient's INR values remained in the therapeutic range. Multiple variables must be examined when assessing INR values, as many things interact with warfarin. For example, tobacco use, alcohol consumption, and changes in vitamin K intake can affect the INR. Since this patient did not use tobacco or consume alcohol and had a fairly consistent dietary intake of vitamin K, these variables were ruled out as influencing the INR. In this case, the changes in his INR values corresponded to the addition or deletion of prednisone. CONCLUSION: A patient's INR values increased after the addition of prednisone to his warfarin regimen.     

Prolonged anticoagulation after discontinuation of argatroban and warfarin therapy in an obese patient with heparin-induced thrombocytopenia

A 32-year-old, morbidly obese African-American woman developed bilateral pulmonary emboli 12 days after undergoing Roux-en-Y gastric bypass surgery. Three days later, after receiving heparin and warfarin, she developed heparin-induced thrombocytopenia type II (HIT-II). An argatroban 1.5-microg/kg/minute infusion was administered for approximately 2.5 days. The patient also received four doses of warfarin, totaling 37.5 mg. The argatroban infusion was discontinued early on hospital day 6, at which time the patient's international normalized ratio (INR) was 4.36 and activated partial thromboplastin time (aPTT) 85.9 seconds. Her INR and aPTT values continued to rise after the argatroban was discontinued and peaked 3 days later at 5.28 and 123.6 seconds, respectively. At this time her platelet count had improved from 139 x 10(3)/mm(3) to 543 x 10(3)/mm(3). No additional warfarin was administered before discharge. On hospital day 11, the patient was discharged home with an INR of 4.12 and an aPTT of 67.1 seconds. Her aPTT and INR values remained elevated for 19 days after receiving her last dose of warfarin and for 20 days after argatroban discontinuation. She experienced no bleeding complications from these supratherapeutic coagulation parameters. She resumed treatment with warfarin as an outpatient and completed a 6-month course of anticoagulation without further incident. Clinicians should be aware that coagulation parameters may remain elevated longer than expected after argatroban discontinuation in certain patients taking concomitant warfarin. Patients with liver dysfunction and obesity appear most likely to be affected.     

心脏瓣膜置换术后患者使用质子泵抑制剂对华法林抗凝初期有效性及安全性的影响

目的：研究心脏瓣膜置换术后患者质子泵抑制剂（PPIs）对华法林抗凝初期的有效性及安全性的影响。方法：收集2013年1月至2014年12月在南京鼓楼医院行心脏瓣膜置换术后使用华法林联合PPIs的患者294例,根据术后使用PPIs的种类分为奥美拉唑组和泮托拉唑对照组。回顾性分析两组间PT值、INR值及华法林日剂量的差异,根据不良反应发生率及停药率评估PPIs与华法林联用的安全性。结果：两组间的华法林平均日剂量、INR值首次达标时间和住院期间INR的控制情况差异无统计学意义（P>0.05）。服药第1天和7天的INR值、PT值在两组间均无显著性差异（P>0.05）,第4天奥美拉唑组INR 1.84±0.49、PT（21.3±5.7）s,显著高于泮托拉唑组INR 1.71±0.37、PT（19.7±4.4）s,P<0.05。在INR 1.6~2.2亚组中,两组术后第4天的INR值分布存在显著性差异（P<0.05）。在安全性指标方面,奥美拉唑组的华法林停药率为（46.1%）,显著高于泮托拉唑组（25.25%）,INR>3的次数、栓塞率和出血率在两组间的差异均无统计学意义（P>0.05）。结论：心脏瓣膜置换术后的患者,在服用华法林抗凝的初期,奥美拉唑增强了华法林的抗凝效果,且影响华法林使用的安全性（如增加华法林的停药率）,两药联用时应当严密监测INR值,保证抗凝治疗的安全。     

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.     

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.     

Difficulties in anticoagulation management during coadministration of warfarin and rifampin

The clinical significance of rifampin's induction of warfarin metabolism is well documented, but no published studies or case reports have quantified this interaction with respect to the international normalized ratio (INR). A patient receiving concomitant rifampin and warfarin to treat a mycobacterial infection and intraventricular thrombus, respectively, underwent routine INR testing at a pharmacist-managed anticoagulation clinic to assess his anticoagulation regimen. A 233% increase in warfarin dosage over 4 months proved insufficient to attain a therapeutic INR during long-term rifampin therapy More aggressive titration of the warfarin dosage was needed. In addition, a gradual 70% reduction in warfarin dosage over 4-5 weeks was necessary to maintain a therapeutic INR after rifampin discontinuation, demonstrating the clinically significant offset of this drug interaction. Extensive changes in warfarin dosage are required to attain and maintain a therapeutic INR during the initiation, maintenance, and discontinuation of rifampin.     

Subcutaneous Enoxaparin for Outpatient Anticoagulation Therapy in a Patient with an Aortic Valve Replacement

Low-molecular-weight heparins have been administered for a variety of clinical conditions. A patient with a mechanical aortic valve replacement patient underwent elective transurethral prostatectomy. Anticoagulation was managed with unfractionated heparin immediately preoperatively and postoperatively. Warfarin was begun on postoperative day 1. The patient had a prolonged hospitalization due to subtherapeutic international normalized ratios (INR) despite warfarin administration. Because he intended to leave the hospital against medical advice before therapeutic INR was achieved, enoxaparin 1 mg/kg subcutaneously every 12 hours was prescribed to provide anticoagulation, facilitating discharge and improving the patient's quality of life. Enoxaparin was associated with an approximate saving of $4500 over warfarin. The only adverse event reported was bruising at the injection site.     

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.     

Subcutaneous phytonadione for reversal of warfarin-induced elevation of the International Normalized Ratio.

The efficacy and safety of subcutaneous phytonadione in the treatment of patients with asymptomatic excessive International Normalized Ratio (INR) values secondary to warfarin therapy were evaluated. Patients at an outpatient anticoagulation clinic with an INR of 8 or more but less than 14 were given 1 mg of subcutaneous phytonadione, and patients with an INR of 14 or more but less than 20 received 2 mg. The patients were instructed to withhold warfarin therapy for the next 24 hours and to immediately report any bleeding complications. At subsequent visits, patients with an INR of 8 or more but less than 14 were given an additional 1 mg of subcutaneous phytonadione. Patients with an INR above 4.5 were instructed to withhold warfarin therapy for an additional 24 hours. Seventeen patients received the 1-mg dose (group 1), and four patients received the 2mg dose (group 2). In group 1, the mean INR reduction was 49% at 24 hours and 72% at 48 hours and the INR was below 4.5 in 93% of patients at 48 hours. In group 2, the mean INR reduction was 67% at 24 hours and 85% at 48 hours and the INR was below 4.5 in 100% of patients at 48 hours. In four group-1 patients and one group-2 patient, the INR fell below 2.0 at 48 hours. No patients reported hemorrhagic or thrombotic complications. Subcutaneous phytonadione safely lowered excessively high INR values caused by warfarin therapy.