华法林对阵发性房颤抗凝治疗的临床观察

目的探讨华法林对老年阵发性房颤抗凝治疗的有效性和安全性。方法将126例65岁以上的阵发性房颤患者,随机分成华法林组（n＝65）和阿司匹林组（n＝61）。华法林组口服华法林进行抗凝治疗,初始剂量3mg／d国际标准化比值（INR）2．0～3．0,根据INR监测情况调整剂量,随访分析患者终点事件和出血事件的发生及与抗强度的关系并与阿司匹林组（口服阿司匹林200mg／d）作对照分析。结果随访6～24个月,华法林平均剂量（3．5±0．69）mg。用药期间发生血栓栓塞华法林组为3例（4．61％）,阿司匹林组为9例（17．64％）,2组比较差异有统计学意义（P〈0．05）;2组出血发生率差异无统计学意义[华法林组4例（6．15％）,阿司匹林组4例（6．56％）（P〉0．05）;2组低危亚组发生血栓栓塞差异无统计学意义[华法林组1例（4．34％）,阿司匹林组3例（15．00％）（P〉0．05）,而2组高危亚组发生血栓栓塞差异有统计学意义[华法林组2例（4．76％）,阿司匹林组6自（14．63％）]（P〈0．05）,而各亚组出血发生率差异均无统计学意义（均P〉0．05）。结论阵发性房颤患者应用华法林抗凝INR维持在2．0～3．0是有效安全的。有必要对确诊的老年阵发性房颤患者进行危险因素分层,65岁以上具备高危因素的老年阵发性房颤患者需应用华法林抗凝治疗。     

华法林对老年持续性房颤患者抗凝治疗的有效性及安全性观察

目的:探讨华法林用于老年持续性房颤患者抗凝治疗的有效性及安全性。方法:入选符合本研究标准的138例老年持续性房颤患者,随机分为两组,华法林组(治疗组)69例,男41例,女28例,以华法林3mg作为起始剂量,按研究设计在不同时点检测国际标准化比值。阿司匹林组(对照组)69例,阿司匹林300mg/d,晚饭后即刻服用,每月随访1次。观察两组不良反应的发生情况。结果:治疗组7~15d(平均10.0±4.8d)国际标准化比值达到1.5~3.0,其比值在1.8~2.5占91.3%。治疗组发生出血2例(2.9%),脑梗死2例(2.9%),上腹不适2例(2.9%)。对照组发生出血2例(2.9%),脑梗死11例(16.2%),上腹不适10例(14.5%)。治疗组脑梗死、上腹不适的发生率低于对照组(P<0.05),两组间出血发生率无统计学差异(P<0.05)。结论:对老年持续性房颤患者应用华法林抗凝治疗能降低中风及上腹部不适的发生率,既有效又安全。     

老年非瓣膜病性心房颤动患者华法林钠抗凝疗效及安全性研究

目的探讨老年非瓣膜病性心房颤动（AF）患者华法林钠（华法林）抗凝治疗的安全性和有效性。方法160例老年（≥75岁）非瓣膜病性持续性AF患者,随机分入调整剂量华法林组和阿司匹林（300mg／d）组。观察国际标准化比值（INR）1．80～2．50时华法林剂量、血栓栓塞事件与出血风险。结果INR1．80～2．50时华法林剂量1．43～3．57mg／d,平均（2．373±0．304）mg／d。160例患者中,发生血栓栓塞13例（8．1％）。其中华法林组2例（2．5％）,阿司匹林组11例（13．8％）,两组间差异有统计学意义（P〈0．05）。轻微出血：华法林组7例（8．8％）,阿司匹林组5例（6．3％）,差异无统计学意义（P〉0．05）;两组均无严重出血。结论严密监测INR情况下,老年AF患者应用华法林抗凝治疗是安全有效的。     

心房颤动患者长期抗凝治疗的临床观察及护理

目的总结对心房颤动（简称房颤）患者长期应用华法林抗凝治疗的护理体会。方法对50例长期应用华法林抗凝治疗的房颤患者，用药前进行基本药物知识宣教，服药期间饮食调节、监测凝血酶原时间（prothrombin time，PT）及其国际标准化比率（international normalized ratio，INR），长期随访并观察抗凝效果及不良反应。结果随访时间（37．3±7．9）个月；INR达标率（2．0～3．0）为88％；不良事件中缺血性、出血性脑卒中各1例，皮下出血3例，口腔黏膜及鼻腔出血1例，长期尿潜血1例。结论华法林抗凝治疗存在一定的风险，主要表现为各系统的出血，应定期监测PT及INR；健康教育有助于避免严重并发症的发生。     

脑梗死合并心房颤动358例抗凝治疗状况分析

目的 了解心房颤动伴脑梗死住院患者抗凝治疗的情况,并比较与指南建议之间的差距.方法 对我院2008年1月至2012年6月收治的358例脑梗死合并心房颤动患者的临床资料进行回顾性分析,重点分析抗凝药物使用情况.结果 358例患者中254例既往有心房颤动史（70.9％）,在脑梗死发病前服用过华法林者11例,占有心房颤动病史患者的4.3％;11例患者国际标准化比值（INR）均＜1.5.出院患者中,20.9％接受华法林抗凝治疗.使用华法林与HAS-BLED评分,MRS评分及抗血小板药物呈负相关（OR分别为-1.974、-0.725、-4.170,P＜0.05或P＜0.01）.出院后给予华法林治疗的患者中,33.8％长期坚持服用华法林,用药剂量中位数为2.5 mg（1.25～3.75 mg）,INR控制在1.5～3.1之间.患者平均1个月（2周～2个月）复查一次凝血常规,INR在治疗目标范围内的时间百分比平均为（61.6±21.2）％.结论 脑梗死合并心房颤动患者的抗凝治疗率和INR达标率均较低,对出血的担忧和监测INR的不便影响了华法林的使用.     

老年持续性心房颤动患者应用华法林抗凝治疗国际标准化比值安全范围的探讨

目的探讨老年持续性心房颤动患者应用华法林抗凝治疗的有效性、安全性及国际标准化比值（INR）范围.方法老年持续性心房颤动患者服用华法林抗凝治疗69例,观察华法林达标时间、维持剂量、安全的INR范围及不良反应.结果华法林达标时间及维持剂量虽有个体差异,但多数（88%）患者在15～30 d内以1.5～2.25 mg/d的量使INR稳定于1.8～2.5,出血发生率最低.结论老年持续性心房颤动患者应用华法林抗凝治疗时,使INR稳定于1.8～2.5既有效又安全.     

老年心房颤动和血栓疾病的华法林抗凝分析

目的探讨老年心房颤动和血栓疾病华法林抗凝治疗。方法总结分析21例（75.7±5.9）岁（64-85岁）的心房颤动（15例）、深静脉血栓（5例）和肺动脉栓塞（1例）患者华法林抗凝治疗的临床资料。华法林起始剂量2．5mg／d，增减0．3125mg-0．625mg／d。INR≥1.8为达标，维持在1．8-2．5，≤3．0。结果（1）19例在服药（10．0±6．0）d、中位数7dlNR达标，2例服药1月、5mg／d≥1wINR不达标而停药。（2）华法林达标时日剂量（2．928±0．591）mg／a高于初始和维持日剂量（2．557±0．681）mg／d，统计学差异显著（P〈0．01，P=0．01）。（3）INR达标时平均2．247±0．488，维持用药期间平均2．454±0．634。（4）治疗期间无INR延长相关的出血事件。结论2．5mg／d的华法林初始剂量及0．3125mg-0．625mg／d的增量调整可使老年房颤和血栓性疾病患者INR在1-3周内平稳扶标,及时调整剂量控制INR存1.8-3.0安全有效。     

华法林在110例房颤中的临床应用观察

目的观察华法林抗凝治疗心房颤动患者的临床疗效及安全性。方法187例老年心房颤动患者随机分为观察组110例和对照组77例。观察组给予华法林口服，维持目标国际标准化比率（INR）2．0～3．0；对照组给予阿司匹林片口服。结果华法林组110例患者华法林维持量1．75～4．15mg／d，平均剂量（2．0±0．75）mg／d，INR平均（3．11±0．68）。华法林观察组和阿司匹林对照组的脑梗死发生率分别为1．82％（2／110）和5．19％（4／77），2组比较差异有统计学意义（P〈0．05）；华法林组出血发生率为2．73％（3／110），阿司匹林组为2．60％（2／77），2组比较差异无统计学意义（P〉0．05）。结论应用华法林抗凝治疗心房颤动可明显减少栓塞事件的发生，维持INR在2．0—3．0之间出血不良反应轻、用药安全。     

心房颤动患者应用华法林抗凝治疗的护理体会

目的 总结对心房颤动（房颤）患者应用华法林抗凝治疗的用药指导和护理体会。方法 96例房颤患者应用华法林抗凝治疗，服用前强化健康教育，服用期间监测凝血酶原时间（PT）及其国际标准化比率（INR），观察其抗凝效果及主要不良反应。结果 经过正规的抗凝治疗和护理，未出现血栓栓塞事件发生，2例患者出现轻微皮下出血，经调整华法林剂量后出血停止，无严重出血发生。结论 服用华法林的房颤患者应定期监测PT及INR。早期发现出血的征象并加强健康教育，可避免严重并发症的发生。     

老年人房颤与NT-ProBNP、左房大小的关系及抗凝现状分析

目的观察老年人房颤与N-末端脑钠肽前体(NT-proBNP)及左房大小的关系,并分析其抗凝现状。方法对120例老年房颤患者的临床资料进行回顾性分析,包括初发、阵发、持续性、持久性、长期持续性房颤患者的NT-proBNP水平、左房内径和抗凝方法。结果 120例老年房颤患者中,初诊房颤占15.0%,阵发性房颤占30.0%,持续性房颤、持久性房颤、长期持续性房颤占55.0%。使用华法林抗凝治疗占41%,房颤发生脑栓塞占9.1%。持续性房颤、持久性房颤、长期持续性老年房颤的患者NT-proBNP明显高于阵发性、初诊房颤患者,其左房内径明显大于阵发性、初诊房颤患者的左房内径。抗凝治疗中华法林组栓塞事件发生率(2.08%)低于阿司匹林组(13.89%),而两组出血事件发生率无显著差异。结论持续性房颤、永久性房颤、长期持续性房颤在老年患者中占主导地位。房颤时间越长,左房内径越大,NT-proBNP也越高。华法林抗凝效果优于阿司匹林,且获益超过出血风险。     

房颤患者华法林抗凝治疗177例

目的回顾性分析心房颤动（房颤）患者的抗凝治疗与卒中情况。 方法调查2015年8月1日至2017年6月30日苏北人民医院住院房颤患者301例的病例资料,记录性别、年龄、主要诊断、合并疾病情况、CHA2DS2-VASc评分、HAS-BLED评分、INR值、华法林剂量、新型口服抗凝剂（NOAC）、阿司匹林使用情况、血栓栓塞事件、出血事件情况,分析抗凝治疗的规范性及其与临床后果的关系。 结果住院房颤患者平均年龄（72±11）岁,房颤类型以非瓣膜型房颤为主,占93.7%（282/301）,58.8%的房颤患者采用口服华法林抗凝治疗,4%接受NOAC抗凝治疗。华法林抗凝治疗组缺血性卒中发生率显著低于未抗凝治疗组差异具有统计学意义（13.0% vs 20.5%,P=0.025）。瓣膜型和非瓣膜型房颤患者华法林抗凝治疗后INR达标（INR 2.0~3.0）的比率分别为15.8%和7.1%。 结论为了达到更好的房颤患者卒中预防效果,需进一步加强华法林抗凝治疗的教育和监测。     

Enhanced hypoprothrombinemia with warfarin due to azithromycin

OBJECTIVE: To report a case of probable azithromycin-warfarin drug interaction with enhanced hypoprothrombinemic effect of warfarin. CASE SUMMARY: An 83-year-old African American man stabilized on warfarin therapy (10 mg on Wednesdays, 7.5 mg on other days) developed a prolonged prothrombin time one day after starting azithromycin 500 mg. The elevated prothrombin time normalized 3 days after azithromycin was discontinued. After the initial increase in the international normalized ratio, the absence of any significant confounding factors affecting the anticoagulant effect of warfarin in our patient and the numerous reports of such interactions indicate that an interaction between azithromycin and warfarin may have been responsible for the elevated prothrombin time seen in this patient. An objective causality assessment revealed that the adverse event was probably related to the combination of these drugs. DISCUSSION: Azithromycin, unlike erythromycin and clarithromycin, is not known to inhibit the cytochrome P450 enzyme system and is presumed to be the macrolide of choice in patients already on warfarin. However, previously reported cases of azithromycin-warfarin interactions support the possibility that azithromycin does interact with warfarin, although the exact mechanism is not understood. CONCLUSIONS: Azithromycin may interact with warfarin and enhance its hypoprothrombinemic effects. This effect may be delayed for 4-8 days after a course of azithromycin has been completed. Periodic monitoring of the prothrombin time is recommended when using azithromycin in patients taking warfarin.     

No increased bleeding events with continuation of oral anticoagulation therapy for patients undergoing cardiac device procedure

Background: Switching warfarin for heparin has been a practice for managing periprocedural anticoagulation in high‐risk patients undergoing device‐related procedures. We sought to investigate whether continuation of warfarin sodium therapy without heparin bridging is safe and, when it is continued, the optimal international normalized ratio (INR) without increased bleeding risk at time of device‐related procedure. Methods and Results: We retrospectively studied 766 consecutive patients taking warfarin long term who underwent device‐related procedures. Patients were grouped by treatment: discontinued warfarin (?warfarin, n = 243), no interruption of warfarin (+warfarin, n = 324), and discontinued warfarin with heparin bridging (+heparin, n = 199). The study primary endpoint was systemic bleeding or formation of moderate or severe pocket hematoma within 30 days of the procedure. Thirty‐one (4%) patients had bleeding events, including pocket hematoma in 29 patients. The bleeding events occurred more often for +heparin (7.0%) than ?warfarin (2.1%) or +warfarin (3.7%, P = 0.029). For +warfarin group, INR of 2.0–2.5 at time of procedure did not increase bleeding risk compared with INR less than 1.5 (3.7% vs 3.4%; P = 0.72), but INR greater than 2.5 increased the bleeding risk (10.0% vs 3.4%; P = 0.029). Concomitant aspirin use with warfarin significantly increased bleeding risk than warfarin alone (5.6% vs 1.4%, P = 0.02). Median length of hospitalization was significantly shorter for +warfarin than +heparin (1 vs 6 days; P < 0.001). Conclusion: Continuation of oral anticoagulation therapy with an INR level of <2.5 does not impose increased risk of bleeding for device‐related procedures, although precaution is necessary to avoid supratherapeutic anticoagulation levels. (PACE 2011; 34:868–874)     

Surreptitious superwarfarin ingestion with brodifacoum

Physicians must have a high index of suspicion when patients have unexplained prolongation of the prothrombin time and bleeding in the absence of detectable warfarin. Several common rodenticides contain modified versions of warfarin that are not detectable in standard warfarin assays. We present a case of surreptitious brodifacoum ingestion in a patient who had years of unexplained bleeding and negative warfarin levels.     

Interaction of amiodarone with racemic warfarin and its separated enantiomorphs in humans

To evaluate a stereoselective interaction for amiodarone and racemic warfarin, we performed a prospective study with its separated enantiomorphs. Single oral doses of racemic warfarin, 1.5 mg/kg, were administered to six normal subjects, with and without oral amiodarone, 400 mg daily, for the hypoprothrombinemic duration. Both the hypoprothrombinemia (P less than 0.001) and plasma warfarin concentrations (P less than 0.01) were significantly increased. The experiments were repeated separately with the R- and S-warfarin enantiomorphs. S-warfarin with amiodarone significantly increased both the hypoprothrombinemia (P less than 0.001) and plasma warfarin concentrations (P less than 0.01). R-warfarin with amiodarone significantly increased both the hypoprothrombinemia (P less than 0.001) and plasma warfarin concentrations (P less than 0.001). Thus amiodarone augmented the anticoagulant effect nonstereoselectively by reduced metabolic clearance of both warfarin enantiomorphs. Amiodarone and racemic warfarin can be a dangerous combination, particularly when either drug is added to a stabilized regimen of the other drug, unless the prothrombin times are monitored carefully.     

Potentiation of warfarin anticoagulation associated with topical methyl salicylate

OBJECTIVE: To report a case of international normalized ratio (INR) elevation resulting from the administration of topical methyl salicylate in a patient whose INR was previously stable while she received warfarin anticoagulation. CASE SUMMARY: A 22-year-old white woman presented with an INR of 12.2 after applying a topical pain-relieving gel to her knees daily for eight days. The potentiation of the warfarin anticoagulation was attributed to the low-dose methyl salicylate contained in the product. DISCUSSION: Methyl salicylate is systemically absorbed through the skin in measurable amounts, and may increase warfarin action by affecting vitamin K metabolism or by displacing warfarin from protein-binding sites. While several investigators have reported this interaction with use of high-dose methyl salicylate, this case indicates that a significant interaction can occur with the use of lower topical doses of methyl salicylate as well. CONCLUSIONS: Healthcare providers and patients taking warfarin must be aware of the potential hazard of using topical methyl salicylate in combination with warfarin.     

海南省黎族与汉族持续性心房颤动患者CYP2C9^*3基因多态性差异

目的:分析罹患持续性心房颤动的海南省黎族与汉族患者细胞色素P450酶2C9^*3(CYP2C9^*3)基因多态性分布,评估CYP2C9^*3基因多态性对患者稳定服用华法林剂量的影响。方法:选取2017年1月至2018年12月于海南医学院第二附属医院就诊的罹患持续性心房颤动的海南省黎族患者100例为研究组,同期海南医学院第二附属医院持续性心房颤动的汉族患者100例为对照组。记录两组研究对象的血清华法林浓度、国际标准化比率(international normalized ratio,INR)达标时间、华法林平均日剂量及总剂量;提取两组基因组DNA,采用扩增阻滞突变体系-聚合酶链式反应技术(amplification refractory mutation system,ARMS-PCR)对CYP2C9^*3基因位点进行基因分型。结果:研究组患者A/A与A/C基因型及等位基因A频率显著低于对照组(P<0.05),C/C基因型及C频率显著高于对照组(P<0.05)。两组不同基因型患者华法林稳定剂量及血清华法林浓度存在差异,均为A/A型最大(P<0.05),而A/C型与C/C型无差异(P>0.05);研究组A/A基因型患者华法林稳定剂量及血清华法林浓度低于对照组(P<0.05),但两组A/C与C/C基因型患者华法林稳定剂量及血清华法林浓度均无差异(P>0.05)。A/A基因型黎族持续性心房颤动患者的INR达标时间、华法林平均日剂量及总剂量最高,C/C基因型最低,A/C基因型次之(P<0.05)。结论:CYP2C9基因多态性与持续性心房颤动的海南省黎族患者稳定服用华法林剂量密切相关,C/C型CYP2C9基因持续性心房颤动的海南省黎族患者INR达标时间、华法林平均日剂量及总剂量更低。     

超高龄心房颤动患者华法林抗凝过程中心血管不良事件的观察

目的: 观察超高龄房颤患者采用不同强度华法林抗凝后的心血管不良事件发生情况,探讨此类患者国际标准化比值(international normalized ratio,INR)的合理范围,为临床提供依据。方法: 将108例超高龄房颤患者（年龄≥80岁）按INR值分为中等强度抗凝组（56例）和低等强度抗凝组（52例）;低等强度抗凝组的INR维持在1.40~1.80;中等强度抗凝组的INR维持在1.81~2.50。随访（1.8±1.2）年,观察发生主要终点事件（缺血性卒中、全身性栓塞）、次要终点事件（非致命性心肌梗死、全因死亡联合终点）、安全性终点事件（致命性出血、严重出血和轻度出血）的情况。结果: 随访期间,中等强度抗凝组中有3例患者发生栓塞,发生率为5.36%;低等强度抗凝组中有6例发生栓塞,发生率为11.54%,均为脑卒中,2组间差异有统计学意义（P<0.05）。低等强度抗凝组中2例、中等强度抗凝组中3例患者出现眼结膜、鼻出血等不良反应,但均无严重出血,2组间出血发生率差异无统计学意义（P>0.05）。结论: 超高龄房颤患者应用华法林,INR维持在1.81~2.50是安全、有效的。     

Successful anticoagulation with dalteparin in a patient with mechanical heart valves

BACKGROUND: Standard thromboprophylaxis of patients with mechanical heart valves is achieved using warfarin. In certain patients this may be very difficult; thus, alternative pharmacotherapy must be used. OBJECTIVE: To report a case of a patient who successfully used dalteparin, a low-molecular-weight heparin, for anticoagulation. CASE SUMMARY: A 58-year-old white woman with mechanical aortic and mitral heart valves initially received warfarin for anticoagulation. Thromboprophylaxis was very challenging. Her international normalized ratios (INRs) were erratic and occasionally responded paradoxically to changes in dose. Finally, she experienced a left hemispheric stroke when her INR was extremely subtherapeutic. Subsequently, despite best efforts, her INR again was subtherapeutic; warfarin was discontinued and dalteparin was initiated with daily self-administered subcutaneous injections of 16 000 units. No complications have arisen since initiation of the new pharmacotherapy approximately 18 months ago. DISCUSSION: The use of low-molecular-weight heparin for the treatment and prevention of venous thromboembolism is well described. There are few reports of its use for thromboprophylaxis of patients with mechanical heart valves. Our patient has been managed successfully with dalteparin. CONCLUSIONS: Dalteparin was effectively and safely used for the thromboprophylaxis of a patient with mechanical heart valves whose anticoagulation was previously difficult to manage with warfarin. Dalteparin deserves further study in patients who are unable to tolerate warfarin.