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。     

非诺贝特与华法林相互作用致血尿1例及文献复习

目的 探讨非诺贝特对华法林抗凝作用的影响、作用机制和处理方法。方法 1位78岁老年男性患者长期稳定服用华法林抗凝治疗,在服用非诺贝特2周后出现咳血、血尿和左下肢疼痛,急诊查INR值为5.9,予停用华法林、肌注维生素K1 10 mg处理后出院,随后根据INR值调整华法林周剂量下降40%后INR值达到稳定,半个月后患者因肌痛停用非诺贝特,INR值连续2周持续下降,调整华法林剂量至接近服用非诺贝特前。结果 患者在稳定的华法林治疗剂量基础上加用非诺贝特后,增加了华法林的抗凝效果。非诺贝特蛋白结合率高,可能把与白蛋白结合的华法林置换下来,导致抗凝效果增强;非诺贝特也是轻到中度的CYP2C9抑制剂,CYP2C9为S型华法林的代谢酶。这2种作用合起来可增强华法林的药效。结论 在长期华法林稳定抗凝治疗的情况下加用非诺贝特后,建议连续监测INR值并考虑经验性降低华法林剂量20%,之后根据INR值继续调整剂量至稳定。     

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。     

华法林引起脑出血死亡一例分析

抗凝药华法林用于老年患者时应特别注意严重出血的不良反应,我们结合华法林使用不当一临床实例,分析如下. 患者女,72a,5年前因患"病态窦房结综合征"安装永久性心脏起搏器,后长期服用肠溶阿斯匹林0.1 g,qd.5年中2次因半身不遂、脑梗死住院,治疗后无明显后遗症.2003年11月27日以"突发左侧肢体无力14h伴头晕"主诉入院.入院诊断:①脑梗死;②冠状动脉粥样硬化性心脏病、心房颤动、永久性心脏起搏器植入术后、心功能不全2级;③高血压病3级;④2型糖尿病.对症治疗后病情相对稳定,查血常规正常、肝功能除Alb 26.3 g·L-1外余未见异常、PT(凝血酶原时间)12.3 s、INR(国际标准化比值)0.97.遂停用阿斯匹林,改服华法林(香港合资新乡中杰药业有限公司)3 mg,qd.服用3 d后测INR 1.41,调整华法林至4 mg,qd.5 d后测INR 5.56,脑出血死亡.患者长期服用的药物还有:格列齐特80 mg,qd;伏格列波糖0.2 mg,tid;培哚普利4 mg,qd;比索洛尔2.5 mg,bid.     

房颤患者应用华法林抗凝治疗的临床体会

目的探讨房颤患者应用华法林抗凝治疗的疗效。方法用药前测INR1次,每天服用1次华法林,初始剂量2．5—3．0mg／d,应用华法林3d后复查INR,以后每天监测,根据INR调整剂量,每次0．5mg为调整单位。若INR连续2d稳定在2．0～3．0之间,每周检测2～3次,以后每周检测1次,1个月后改为每月检测1次,6个月后改为每2个月检测1次。若有出血等不良反应和栓塞并发症发生时即查血浆凝血酶原时间（PT）、INR。结果52例患者均得到随访,随访时间6个月～4年,华法林维持量为（3．0±0．05）mg／d。随访期间血栓栓塞并发症及不良反应脑栓塞2例,其中1例为既往发生过脑卒中的高血压患者;1例为瓣膜病患者;脑出血2例,为人工瓣膜患者,因咳嗽、咯痰、发热,在院外静点头孢曲松钠3．0g（1次／d）,1周后复查INR为8．45;黑便1例、血尿1例、球结膜出血2例、皮下出血2例、牙龈出血2例,经调整华法林剂量及对症处理后出血症状消失。结论心房颤动一旦确诊,又无抗凝禁忌,应常规给予华法林抗凝治疗,以尽早达到治疗效果。     

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。     

1例双瓣置换术后血小板减少患者华法林合理用药分析

目的探讨双瓣置换术后并发血小板减少的患者的抗凝治疗策略,为临床药师参与抗凝治疗提供参考。方法临床药师回顾性分析1例双瓣置换术后患者血小板减少的原因,结合药代动力学知识和相关文献资料,确定华法林初始剂量和目标国际标准化比值(INR),优化抗凝方案。结果患者血小板计数逐渐恢复正常;华法林抗凝治疗以5 mg为初始剂量,目标INR为1.8~2.5。经过五次剂量调整后以3.125 mg的维持剂量带药出院,出院时INR为1.5。结论临床药师参与可为患者提供更加安全、有效的治疗方案。     

375例口服华法林抗凝治疗患者的跟踪调查

目的：通过定期跟踪随访,调查华法林抗凝治疗的现状。方法：选择华法林抗凝治疗住院患者,且出院后继续抗凝治疗至少3个月,收集患者住院期间的临床资料,并在出院后定期跟踪随访。结果：在375例接受随访的患者中,234例达到稳定抗凝治疗。心脏瓣膜置换患者的华法林抗凝治疗依从性最好,其次为静脉血栓和肺栓塞患者,房颤患者的依从性最差。使用华法林首次负荷剂量者更易达到稳定抗凝效果;在发生出血并发症的患者中,女性显著多于男性,且5d内INR达到或超过目标范围的患者比例高。结论：治疗起始阶段的剂量和INR值以及性别是影响华法林达到稳定治疗和出血并发症的主要临床因素。应加强对房颤患者出院后华法林抗凝治疗的指导。     

心脏机械瓣膜置换术后华法林抗凝治疗的研究

目的:探讨心脏机械瓣膜置换术后华法林临床抗凝治疗的影响因素、给药方法以及国际标准化比值(INR)监测。方法:对114例心脏瓣膜置换术后应用华法林抗凝治疗的患者的临床资料进行分析,记录年龄、性别、华法林剂量和INR值等,观察出血、栓塞等不良反应发生情况。结果:华法林维持剂量及达标时间个体差异较大,与年龄、性别、体重无关。华法林维持剂量范围1～6mg·d~(-1),71.1%的患者维持剂量为2.0～4.5mg·d~(-1),INR稳定达标时间为10～21d。结论:华法林抗凝治疗个体差异大,应在严密监测INR值条件下使用。     

心房颤动患者抗凝治疗的体会

目的：探讨华法林在房颤患者抗凝治疗中的标准化比值（INR）,以减少华法林的不良反应。方法：回顾性分析2004年3月～2009年3月使用华法林抗凝治疗房颤患者106例的临床资料。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1.61%、年出血并发症为0.49%,分别低于文献报道的4%及1%。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INR,确保华法林的安全使用。     

Oral anticoagulant drug interactions with statins: case report of fluvastatin and review of the literature

A 67-year-old man receiving a stable maintenance dosage of warfarin experienced an increased international normalized ratio (INR) without bleeding when his atorvastatin therapy was switched to fluvastatin. His warfarin dosage was reduced and his INR stabilized. The fluvastatin was switched back to atorvastatin, and the warfarin dosage was increased to maintain the patient's goal INR. The literature supports a drug interaction between warfarin and fluvastatin due to the strong affinity of fluvastatin for the cytochrome P450 enzyme 2D6. This interaction has not been seen with atorvastatin. Lovastatin also reportedly has caused increases in INR when coadministered with warfarin. It is unclear whether simvastatin interacts with warfarin, but it may increase INRs slightly or increase serum simvastatin levels. One case report describes an interaction between simvastatin and the anticoagulant acenocoumarol, which resulted in an elevated INR. Pravastatin does not appear to interact with warfarin but has caused an increased INR when combined with the anticoagulant fluindione. Thus, until more definitive data are available, clinicians should monitor the INR closely after starting statin therapy in any patient receiving anticoagulation therapy.     

低剂量华法林对心房颤动患者脑卒中和凝血指标的影响

目的 探讨心房颤动患者低剂量长期使用华法林对患者脑卒中和凝血指标的影响。方法 选择2016年1月—2018年12月喀什地区第一人民医院收治的心房颤动患者213例作为研究对象,按照随机数字表法将患者分为3组,每组各71例。对照组患者使用阿司匹林肠溶片,200 mg/d。华法林高剂量组患者在使用华法林钠片前测定抗凝强度国际化标准比率（INR）作为基础值,初始剂量为2.5 mg/d,每隔3~5 d复查IRN,根据IRN调整使用剂量,每次增加0.625 mg,直至复查INR达标,达标时IRN值为2.1~3.0。华法林低剂量组患者使用华法林初始量为1.25 mg/d,每隔3~5 d复查IRN,达标时IRN值为1.5~2.0。根据IRN调整使用剂量,如果INR<1.5,每次增加0.625 mg,直至复查INR达标;如果INR>2.1,将华法林剂量减少0.625 mg。INR不稳定时,连续达标2次后以该剂量作为维持剂量,每月复查1次,直至INR达标。3组均治疗随访18个月。观察并比较两组患者的脑卒中发生情况、凝血指标、华法林用量、达INR标准时间和不良反应发生情况。结果 随访后,华法林高剂量组脑卒中发生率为2.82%,华法林低剂量组为4.23%,均明显低于对照组的14.08%,组间差异具有统计学意义（P<0.05）。治疗后,3组活化部分凝血活酶时间（APTT）、凝血酶原时间（PT）均明显延长（P<0.05）,华法林高剂量和低剂量APTT、PT显著优于对照组,组间差异具有统计学意义（P<0.05）。华法林低剂量组华法林使用量和INR达标准值时间均明显低于华法林高剂量组（P<0.05）。治疗期间,华法林高剂量组出血、腹部不适等不良反应发生率为9.86%,华法林低剂量组为5.63%,均明显低于对照组的29.58%（P<0.05）。结论 心房颤动患者长期使用低剂量华法林能够有效的达到预防脑卒中的效果,其疗效与标准抗凝强度相当,且明显优于阿司匹林,具有较高的临床应用价值,可推广使用。     

Potential glucosamine-warfarin interaction resulting in increased international normalized ratio: case report and review of the literature and MedWatch database

We describe a 71-year-old man who had received warfarin 7.5 mg/day for 5 years for atrial fibrillation, which had maintained his international normalized ratio (INR) within a narrow range of 2.5-3.2. During this 5-year period, he had also been treating himself with the supplement glucosamine hydrochloride 500 mg-chondroitin sulfate 400 mg twice/day for arthritis. The patient then increased his dosage of glucosamine to 1500 mg and chondroitin to 1200 mg twice/day; his INR previous to this change was 2.3. Approximately 3 weeks later, his INR increased to 3.9. His supplement dosage was reduced to glucosamine 750 mg-chondroitin 600 mg/day; a repeat INR done 16 days later was 4.7. The supplement was then stopped, and his warfarin schedule was changed to 7.5 mg every other day alternating with 3.75 mg every other day. Sixteen days later, his INR was 2.6. This case report suggests that a potential interaction exists between warfarin and glucosamine that is associated with an increase in the INR. We therefore performed a pharmacovigilance survey of spontaneously reported adverse events in warfarin-treated patients concomitantly exposed to glucosamine, glucosamine-chondroitin sulfate, or chondroitin sulfate and present a literature review of this apparent drug-drug interaction. Using the United States Food and Drug Administration (FDA) MedWatch database, 20 reports of glucosamine or glucosamine-chondroitin sulfate use with warfarin associated with altered coagulation (manifested by increased INR, or increased bleeding or bruising) were identified. In some cases, a decrease in the supplement dosage was followed by a return of the INR to the previous therapeutic range. Similarly, a decrease in warfarin dosage was followed by a decrease in INR in one patient who received long-term warfarin therapy. One report described an intraventricular bleed and subdural hematoma, which resulted in a persistent vegetative state. The World Health Organization (WHO) adverse drug reactions database documented 21 spontaneous reports of increased INR associated with glucosamine use, 17 of which resolved when glucosamine was stopped. We located one published case report of concomitant use of glucosamine-chondroitin sulfate potentiating the effect of warfarin. In aggregate, the reports from the FDA and WHO, the published case report, and our case report suggest that the use of warfarin and glucosamine may lead to an increased INR. Patients should be advised that the use of the two products may cause an increase in INR, and they should inform their health care provider if they consume glucosamine. More information is necessary to define this interaction.     

临床药师对1例妊娠甲状腺功能亢进患者的药学监护

目的:为妊娠甲状腺功能亢进患者用药提供参考。方法:临床药师通过参与妊娠甲状腺功能亢进患者治疗用药方案的制订,建议将富马酸比索洛尔片2.5 mg、qd、po,丙硫氧嘧啶50 mg、tid、po改为甲巯咪唑10 mg、qd、po,普萘洛尔10 mg、tid、po。结果:医师部分接受了药师的建议,改为甲巯咪唑10 mg、qd、po。2周后复查甲状腺功能较前改善,继续用药4周后甲状腺功能示血清游离三碘甲腺原氨酸(FT3)6.12 pmol/L、血清游离甲状腺素(FT4)22.61 pmol/L、促甲状腺激素(TSH)2.26μIU/ml,停用比索洛尔,甲巯咪唑改为5 mg、qd、po。继续用药1月后复查甲状腺功能FT3 5.5 pmol/L、FT4 20.97 pmol/L、TSH 2.63μIU/ml,停用甲巯咪唑。此后保持每4周定期复查甲状腺功能,均维持在正常范围,未再出现怕热多汗等症状,后自然分娩一健康女婴。结论:临床药师可通过规范的对症治疗改善妇女妊娠及胎儿的结局。     

阿奇霉素对大鼠灌服华法林的药效学和药动学的影响

目的：研究抗生索阿奇霉素对大鼠灌服华法林的药效学指标凝血酶原时间（PT）和国际标准化比值（INR）以及药动学指标血药浓度的影响。方法：将SD大鼠随机分成两组：单用华法林组（A组）和华法林＋阿奇霉素合用组（B组）,每组大鼠灌胃给予华法林0．2mg·kg^-1,每日1次,连续613,其中B组大鼠在第6日最后1次灌胃给予华法林后立即腹腔注射阿奇霉素80mg·kg^-1,且开始计时,分别于0．25、0．5、1．5、2．5、3．5、5、7、10、13小时采血,测定PT,计算INR。并建立HPLC法,测定华法林血药浓度。结果：从5小时开始,B组大鼠的胛值较A组显著增大（P〈0．05）,INR值最高可达7．5;B组大鼠的华法林药动学参数咒。较A组显著延长（P〈0．01）,其他药动学参数无显著性差异;两组大鼠的INR-C曲线都呈逆时针走向,且B组的逆时针效应更甚。结论：阿奇霉素与华法林合用可发生药效学和药动学相互作用,增强华法林的抗凝作用,增加用药者的出血风险,故临床上两药合用时应密切监测用药者的INR值,避免严重不良反应的发生。     

Effect of carbamazepine initiation and discontinuation on antithrombotic control in a patient receiving warfarin: case report and review of the literature

A 72-year-old Caucasian woman with paroxysmal atrial fibrillation had been taking warfarin therapy for 5 years with a stable international normalized ratio (INR). Her dentist then prescribed carbamazepine 200 mg/day to control facial nerve pain. At her next physician visit about 2 weeks after the start of the carbamazepine, the patient's INR had dropped from 3.3 to 1.3; she reported no contributing changes in her diet or warfarin dosage, nor had she taken other interacting drugs. Her warfarin dosage was increased, and the INR returned to the target range of 2.0-3.0 approximately 2 months later. The patient's INR remained stable for approximately 6 more months, until she had facial surgery. During that time, her warfarin was discontinued for 5 days, and the patient had stopped taking the carbamazepine because she had no pain. One month later, her INR increased from 2.2 to 3.6. She did not experience any thrombotic or hemorrhagic episodes. Warfarin undergoes hepatic metabolism through cytochrome P450 2C9, and carbamazepine induces this isoenzyme. Inducing warfarin metabolism necessitates an increase in the warfarin dosage to maintain the INR in the therapeutic target range. To our knowledge, this is the first report documenting the effect of the carbamazepine initiation and discontinuation in a patient receiving anticoagulation therapy with warfarin. In patients taking warfarin, clinicians should monitor the INR closely when carbamazepine is started or discontinued, or when either dosage is changed.     

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。     

Study on warfarin plasma concentration and its correlation with international normalized ratio

A sensitive high-performance liquid chromatographic (HPLC) method was developed for warfarin determination in plasma of patients who undertook cardiac valve replacement and were on anticoagulation with warfarin. The method described proved to be accurate, sensitive, easy to perform, reproducible and specific for plasma warfarin measurement with relative standard deviation (R.S.D.) of <5.27% for inter-day and <6.89% for intra-day. The assay was linear in warfarin concentration ranges of 0.12-3 microg/ml (r=0.9995) with mean recovery of 94.6%. The mean warfarin plasma concentration of 58 patients with heart valve replacement within 1 month of post operation was 567.6+/-122.3 ng/ml. The anticoagulant effect of the drug was monitored by international normalized ratio (INR). The correlation of warfarin dosage and concentration with INR was analysed, and the coefficients were 0.21, 0.1相似文献   

苯溴马隆与华法林合用致房颤患者国际标准化比值升高一例报告

1例77岁男性患者,因高血压病、慢性阻塞性肺疾病急性加重期、双下肢凹陷性水肿入院治疗,入院后给予强心,降压治疗,利尿降低心脏负荷并改善水肿,同时给予抗感染对症治疗。患者4年前确诊＂心房纤颤＂,一直规律服用华法林（po,1.5 mg,qd）,入院后第2天测得国际标准化比值（INR）1.35,住院期间因尿酸偏高,入院后第33天加服苯溴马隆（po,50 mg,qd）降尿酸治疗。服用苯溴马隆后第3天上午INR升至3.41,下午升至3.71。第4天停用苯溴马隆,停用2 d后INR降至2.1。     

Warfarin and acetaminophen interaction

A 74-year-old man who was receiving warfarin for atrial fibrillation experienced an abrupt increase in his international normalized ratio (INR) after taking acetaminophen. To investigate this effect, the patient's anticoagulation therapy was stabilized, and he was given acetaminophen 1 g 4 times/day for 3 days. His INR rose from 2.3 before receiving acetaminophen to 6.4 on the day after acetaminophen was discontinued. Warfarin was stopped for 2 days, and the patient's INR returned to 2.0. Warfarin was restarted at the same dosage, and his INR remained within 2.0-3.0 for 6 months. Factor VII activity decreased from 29.4% before acetaminophen therapy to 15.5% when his INR was 6.4, and factor X activity fell from 27.0% to 20.2%. His warfarin plasma concentration was 1.54 microg/ml before acetaminophen compared with 1.34 microg/ml when his INR was 6.4. No significant changes in drug intake, clinical status, diet, or lifestyle were noted. Changes in INR of this magnitude with the addition of another drug during stable anticoagulation therapy suggest a drug interaction. The lack of an increase in warfarin plasma concentration associated with the increased INR suggests a possible pharmacodynamic mechanism for this interaction. Acetaminophen or a metabolite may enhance the effect of oral coumarin anticoagulants by augmenting vitamin K antagonism. Thus, the anticoagulant effect of warfarin may be significantly elevated after only a few days of acetaminophen therapy. Patients receiving warfarin should be counseled to have their INR monitored more frequently when starting acetaminophen at dosages exceeding 2 g/day.