Comparison of cost, effectiveness, and safety of injectable anticoagulants used for thromboprophylaxis after orthopedic surgery.

PURPOSE: The cost, effectiveness, and safety of injectable anticoagulants used for thromboprophylaxis after orthopedic surgery were compared. METHODS: This retrospective, observational, cross-sectional, cohort analysis of inpatient billing data was conducted from the institutional perspective. Patients who received dalteparin, enoxaparin, fondaparinux, or unfractionated heparin after orthopedic surgery were included in the analysis. The primary outcome measure was the mean aggregated cost per patient treated with each injectable anticoagulant. Secondary outcomes included the percentages of patients in each treatment group who had a venous thromboembolism (VTE) or major bleeding episode. RESULTS: Mean total adjusted costs were significantly lower for fondaparinux ($18,019) compared with other anticoagulants, with unfractionated heparin being the most costly ($20,835). Relative adjusted cost differences were 1.4% (p = 0.0127), 1.8% ( p = 0.0105), and 14.6% (p < 0.0001) higher for enoxaparin, dalteparin, and unfractionated heparin, respectively, compared with fondaparinux. Significantly fewer fondaparinux-treated patients had a VTE event compared with the other treatment groups. The use of dalteparin was associated with fewer major bleeding events, and no significant differences in the rate of major bleeding events were observed among groups treated with fondaparinux, enoxaparin, or unfractionated heparin. CONCLUSION: A retrospective analysis of inpatient billing data showed that, among orthopedic surgery patients, fondaparinux was associated with lower institutional cost and a lower frequency of VTE than were dalteparin, enoxaparin, and unfractionated heparin. Dalteparin was associated with a lower rate of major bleeding events than was fondaparinux, but there were no significant differences in such events among fondaparinux, enoxaparin, and unfractionated heparin.     

Anticoagulation strategies for treatment of ischemic stroke and antiphospholipid syndrome: case report and review of the literature

A 49-year-old Caucasian man with antiphospholipid syndrome who experienced an ischemic stroke required multidisciplinary decisions regarding acute and long-term care. The patient first received warfarin and unfractionated heparin, followed by low-molecular-weight heparin. However, he developed complications from these drugs (warfarin-induced necrosis and heparin-induced thrombocytopenia), resulting in thigh necrosis and multiple additional cerebral and peripheral infarcts. His condition improved after warfarin and the heparins were discontinued, and a direct thrombin inhibitor, argatroban, was given intravenously for acute treatment. Argatroban is the only anticoagulant known to be safe in patients who experience an acute ischemic stroke in the setting of heparin-induced thrombocytopenia. For long-term anticoagulation, fondaparinux, an indirect, selective factor Xa inhibitor, was given subcutaneously. The patient received intravenous dexamethasone, later changed to azathioprine, for immunomodulatory treatment. He had significant improvement in his neurologic deficits without recurrent events over the next 18 months. Management of anticoagulation therapy in patients with antiphospholipid syndrome is complex and challenging, and therapeutic strategies need to be evaluated further.     

小剂量阿加曲班在连续性肾脏替代治疗中的疗效和安全性分析

目的:探讨小剂量阿加曲班在高出血风险患者行连续性肾脏替代治疗(CRRT)中的抗凝效果以及安全性。方法:入选高出血风险患者给予阿加曲班0.1~0.3μg·(kg·min)^-1抗凝,评估凝血指标、滤器管路凝血事件、全身出血事件以及血象和肝功能指标。结果:共入选28例高出血风险患者行CRRT397周期,与CRRT前相比:治疗期间和CRRT结束后0~3h的活化部分凝血活酶时间(APTT)差异有显著性(P=0.000);CRRT结束3h后APTT的差异无显著性。根据CRRT上机2~4h的APTT以及血液净化管路动静脉压情况调整阿加曲班给药剂量共114次,调整剂量后复测APTT较前降低,与CRRT上机2~4h相比,差异有显著性(P=0.034)。CRRT期间发生管路和滤器凝血事件共55周期(13.85%)。阿加曲班抗凝期间发生出血事件6例,其中气道出血3例,皮肤瘀斑2例,消化道出血1例,CRRT期间继续减量使用阿加曲班抗凝未观察到有出血加重事件。结论:APTT与阿加曲班抗凝剂量具有较好的相关性,在CRRT结束后凝血指标较快恢复正常,小剂量阿加曲班对高出血风险患者CRRT期间抗凝治疗具有较好的抗凝效果和安全性。     

比伐卢定与肝素用于儿童及青少年体外膜肺氧合抗凝的有效性与安 全性比较的Meta 分析

目的:系统评价比伐卢定与肝素用于儿童及青少年体外膜肺氧合( ECMO) 抗凝的有效性与安全性。方法:计算机检索 PubMed、the Cochrane Library、EMBase、万方、中国知网(CNKI)及维普(VIP)等数据库,搜集有关比伐卢定与肝素用于儿童及青 少年ECMO 抗凝的临床研究,检索时限均为建库至2022 年9 月5 日,由2 名研究者独立筛选文献、提取资料并采用纽卡斯尔-渥 太华量表(NOS)对纳入文献进行质量评估,采用Rev Man 5. 4 软件进行Meta 分析。结果:共纳入6 篇回顾性队列研究,包括246 例 患儿。Meta 分析结果显示,与肝素比较,比伐卢定显著降低儿童及青少年ECMO 抗凝患儿的出血事件(RR=0. 30,95%CI 0. 15~ 0. 64,P =0. 002)及卒中率(RR=0. 39,95%CI 0. 18~0. 84,P =0. 02),但病死率(RR=0. 95,95%CI 0. 70~1. 28)、血栓形成发生率 (RR=0. 94,95%CI 0. 34~2. 61)、ECMO 管路干预发生率( RR = 1. 08,95%CI 0. 53 ~ 2. 19)、生存率( RR = 1. 16,95%CI 0. 90 ~ 1. 49)比较差异均无统计学意义。结论:比伐卢定可以显著降低儿童及青少年ECMO 抗凝患儿的出血事件和卒中率,在改善病 死率、血栓形成发生率、ECMO 管路干预发生率、生存率方面优势不明显。由于纳入的研究均为回顾性队列研究,因此本Meta 分析的证据水平较低,不可避免存在异质性,迫切需要更高质量的随机双盲对照研究予以验证。     

A disease management protocol for outpatient perioperative bridge therapy with enoxaparin in patients requiring temporary interruption of long-term oral anticoagulation

STUDY OBJECTIVE: Traditional perioperative bridge therapy for patients receiving long-term oral anticoagulation involves weight-adjusted intravenous unfractionated heparin (UFH) in the perioperative period during temporary discontinuation of the oral anticoagulant. We sought to determine whether an alternate strategy of outpatient-based perioperative disease management with low-molecular-weight heparin (LMWH) as bridge therapy provides the potential for cost savings. DESIGN: Retrospective review of all clinic notes from an anticoagulation clinic. SETTING: An integrated, staff-model health maintenance organization. PATIENTS: Patients receiving long-term warfarin therapy from January 1998-March 2002 who received perioperative bridge therapy with the LMWH enoxaparin 1 mg/kg twice/day subcutaneously MEASUREMENTS AND MAIN RESULTS: A total of 126 bridge therapy encounters in 84 patients receiving LMWH as perioperative bridge therapy were identified, with 48 of those encounters involving patients with at least one mechanical heart valve. A total of 1108 hospital bed days were saved. Based on 1996 cost estimates, the total approximate cost savings for the 4.25 years of the outpatient bridge therapy program was dollars 903,020. No thrombotic events were reported. Three major hemorrhagic events that required discontinuation of LMWH were reported. CONCLUSION: Outpatient-based disease management protocols and the LMWH enoxaparin as bridge therapy during temporary discontinuation of warfarin for an elective surgical procedure resulted in cost savings of approximately dollars 212,475/year in an integrated health maintenance organization. In addition, this strategy appears both safe and effective.     

Argatroban therapy for antithrombin deficiency and mesenteric thrombosis: case report and review of the literature

Antithrombin deficiency is a hypercoagulable state that can increase the risk for thrombosis, especially in the presence of other procoagulant triggers. Unfractionated heparin and low-molecular-weight heparins may not provide effective anticoagulation since they require antithrombin for activity. Direct thrombin inhibitors, however, work independently of antithrombin. A 21-year-old man with a history of heavy alcohol consumption had thrombosis of the superior mesenteric vein. Infusion with unfractionated heparin was started, and despite repeated boluses and increases to 21 U/kg/hour, the maximum activated partial thromboplastin time reached was 39 seconds. The unfractionated heparin was discontinued, and the direct thrombin inhibitor argatroban was infused at rates of 0.4-0.5 microg/kg/minute. Over the course of several weeks, the patient had numerous operations to remove and repair necrotic bowel. When no further surgery was anticipated, warfarin therapy was started; the argatroban infusion was discontinued when the patient reached the therapeutic target international normalized ratio with warfarin. No recurrent thrombosis or major bleeding occurred. Direct thrombin inhibitors, such as argatroban, seem to be suitable alternatives for acute anticoagulation in patients with antithrombin deficiency.     

A comparison of enoxaparin with unfractionated heparins in patients with coronary heart disease in an emergency department in rural South Indian tertiary care teaching hospital

Aim:Antithrombotic therapy with heparin plus antiplatelets reduces the rate of ischemic events in patients with coronary heart disease. Low molecular weight heparin has a more predictable anticoagulant effect than standard unfractionated heparin, is easier to administer, does not require monitoring and is associated with less ADRs. The purpose of the present study was to evaluate and compare the clinical and cost outcomes of Enoxaparin with a standard unfractionated heparin in patients with coronary heart disease.Results:Compared to unfractionated heparin group of patients, the average prothrombin time was significantly higher (P < 0.0001) whereas hypokalemia was significantly lower (P < 0.02) in enoxaparin group of patients. Even though recurrence of angina and ADRs such as bleeding, nausea, headache and sudden cough occurred less frequently in the enoxaparin group of patients compared to unfractionated heparin group of patients, the differences were not significant.Conclusions:Antithrombotic therapy with enoxaparin plus aspirin was safer and more effective than unfractionated heparin plus aspirin, in reducing the incidence of ischemic events in patients with unstable angina or myocardial infarction in the early phase.KEY WORDS: Anticoagulant, coronary heart disease, enoxaparin, safety, and efficacy, unfractionated heparin     

1例长期服用华法林患者围手术期的抗凝策略

目的：探索长期接受抗凝治疗患者围手术期的抗凝治疗策略,体现临床药师参与药物治疗的作用。方法：回顾临床药师参与1例长期接受华法林抗凝治疗患者围手术期抗凝方案,结合相关的文献资料,从药物的选择、使用时机、剂量、疗程等方面进行分析。结果：临床药师结合药动学知识,制定抗凝方案,最大程度上降低了患者出血和栓塞的风险。结论：围手术期应该至少提前5d停用华法林,并监测国际标准化比值（INR）;术后无继续出血可在12h内开始使用低分子肝素,同时服用华法林,并监测INR,待达标后停用低分子肝素。如果患者要连续进行多次手术,则在整个手术期间建议使用低分子肝素进行抗凝。     

Periprocedural bridging therapy in patients receiving chronic oral anticoagulation therapy

BACKGROUND: In patients receiving chronic oral anticoagulation with vitamin K antagonists (VKAs) it may be necessary to temporarily discontinue VKA therapy to allow surgery or other invasive procedures to be performed, as maintaining treatment may increase the risk of bleeding during the procedure. This, however, creates a clinical dilemma, since discontinuing VKAs may place the patient at risk of thromboembolism. SCOPE: We undertook a systematic narrative review of patients on chronic oral anticoagulation, requiring a periprocedural bridging therapy with heparin during invasive procedures. FINDINGS AND RECOMMENDATIONS: For patients requiring temporary discontinuation of VKA, current guidelines recommend the use of 'bridging' therapy with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) in patients considered to be at intermediate-to-high risk of thromboembolism, such as those with prosthetic heart valves or atrial fibrillation. Recent studies show that LMWHs are associated with low rates of thromboembolism and, when compared with UFH, are as effective and safe as UFH when used as periprocedural bridging therapy in such patients. LMWHs also offer advantages such as ease of administration and predictable anticoagulant effects. Moreover, outpatient-based periprocedural bridging therapy with LMWH has been shown to result in significant cost savings compared with in-hospital UFH. CONCLUSIONS: The decision to provide bridging therapy requires careful consideration of the relative risks of thromboembolism and bleeding in each patient. Based upon the studies reviewed we recommend a therapeutic dose of UFH or LMWH for patients at intermediate-to-high thromboembolic risk requiring interruption of VKA, especially for low bleeding risk procedures. We would like to propose upgrading the American College of Chest Physicians (ACCP) guideline recommendations from 2C to 1C. However, there is still a need for a randomized controlled trial on the efficacy and safety of the available bridging strategies, including heparin and placebo comparators, in preventing thromboembolism for specific patients and procedures.     

Comparison of anticoagulant effects and safety of argatroban and heparin in healthy subjects

STUDY OBJECTIVE: To evaluate and compare the relationship between dosage and coagulation parameters, as well as safety profiles, of ascending bolus and infusion dosages of argatroban versus heparin in three phase I studies. DESIGN: Two randomized, double-blind studies compared argatroban and heparin, and one open-label, dose-escalation study further evaluated argatroban. SETTING: University teaching hospital clinical research unit. PATIENTS: Healthy men (aged 22-62 yrs). INTERVENTION: In the first study, 36 subjects received an argatroban 30-, 60-, 120-, or 240-microg/kg bolus, or a heparin 30-, 60-, 120-, or 240-U/kg bolus for three subjects, then amended to 15, 30, 60, or 120 U/kg. In the second study, 37 subjects received argatroban 1.25, 2.5, 5, or 10 microg/kg/minute with or without a 250-microg/kg bolus, or heparin 0.15, 0.20, 0.25, or 0.30 U/kg/minute with or without a 125-U/kg bolus. In the third study (open-label), nine subjects received an argatroban 250-microg/kg bolus plus an infusion of 15, 20, 30, and 40 microg/kg/minute. MEASUREMENTS AND MAIN RESULTS: When administered as a bolus dose in the first study, argatroban and heparin both produced dose-related increases in activated clotting time (ACT) and activated partial thromboplastin time (aPTT) within 10 minutes of administration. Dissipation of anticoagulant effect was approximately 4-fold faster for argatroban than for heparin. When administered by infusion with or without a bolus in the second study, argatroban, but not heparin, produced predictable dose-related increases in ACT and aPTT that were generally consistent across both effect measures and modes of administration. Effect steady state was attained by five or more subjects per dosing group receiving argatroban (5-9) but typically two or fewer subjects per group receiving heparin (0-7). Furthermore, upon cessation of infusion, anticoagulant effects dissipated faster for argatroban (effect half-life 18-41 min) than for heparin (effect half-life 23-134 min). When argatroban was infused without a bolus, peak and effect steady-state values for ACT and aPTT generally were attained within 1-3 hours. Data from the second and third studies show that for argatroban dosages up to 40 microg/kg/minute, plasma drug concentrations attained at 4 hours of infusion increased linearly with dose, and weight-adjusted plasma clearance was dose independent. In all studies, argatroban and heparin were well tolerated. CONCLUSION: Anticoagulation was more predictable with argatroban than with heparin as measured by ACT and aPTT, with comparable safety profiles.     

Argatroban therapy in heparin-induced thrombocytopenia

Argatroban is a direct thrombin inhibitor approved for anticoagulation in heparin-induced thrombocytopenia (HIT; in several countries) and in patients with or at risk of HIT undergoing percutaneous coronary intervention (PCI; in the USA). HIT is a relatively common extreme prothrombotic condition. When HIT is reasonably suspected, an alternative anticoagulant should be promptly initiated. In historical controlled studies, argatroban reduced new thrombosis, mortality from thrombosis and the composite of death, amputation or thrombosis, without increasing bleeding. With intravenous infusion, advantages include short half-life, easy monitoring and elimination primarily by hepatobiliary (rather than renal) means. In patients undergoing PCI, argatroban with or without glycoprotein IIb/IIIa inhibition leads to high rates of procedural success with low bleeding risk. Herein we review argatroban therapy for HIT and for PCI.     

Use of low-molecular-weight heparin during dental extractions in a medicaid population

BACKGROUND: Evidence-based guidelines recommend against discontinuation of oral anticoagulation therapy during most dental procedures because severe bleeding complications are rare and there is an increased risk for thromboembolic events in patients for whom warfarin therapy is interrupted. Although interruption of oral anticoagulation and bridge therapy with low-molecular- weight heparin (LMWH) may be indicated for high-risk individuals undergoing certain procedures, the use of LMWH in tooth extractions is expensive and often unnecessary. OBJECTIVE: The purpose of this review was to identify and characterize procedural use of LMWH for dental extractions with respect to current consensus recommendations. METHODS: The Idaho Medicaid pharmacy and medical claims database was queried to identify patients with a tooth extraction procedure between February 1, 1998, and January 31, 2005. Patients on warfarin therapy for 2 months before tooth extraction were identified as were claims for LMWH within 30 days before the procedure or 5 days after. Patient profiles were reviewed to determine number of extractions, rate of LMWH use, indication for anticoagulation, and associated drug costs. RESULTS: Of 55,260 Medicaid patients who had a tooth extraction, 518 (0.9%) had received warfarin for at least 2 consecutive months before the tooth extraction procedure. Of these, 31 patients (6%) received LMWH therapy at the time of extraction for a total of 35 procedures. All procedures selected for review carried a low bleeding risk, with an average of 1.3 teeth extracted per procedure. The indications for anticoagulation included 16 procedures (45.7%) involving patients with a history of a thromboembolic event more than 90 days before the procedure, 10 procedures (28.5%) involving patients with a prosthetic valve, 4 procedures (11.4%) involving anticoagulated patients with atrial fibrillation, and 5 procedures (14.2%) involving patients with a history of thromboembolism fewer than 3 months before the procedure. LMWH costs for these 35 extractions totaled $22,294, or an average of $637 per procedure or $474 per extracted tooth. Enoxaparin was used in all but 1 of the procedures, with an average 5-day supply (average 8 enoxaparin units) dispensed per procedure. The costs associated with the required additional drug monitoring, e.g., INR monitoring, were not included in this analysis. CONCLUSION: Although the overall number of dental procedures in anticoagulated patients using LMWH was small in our review, this inappropriate use resulted in avoidable costs to this Medicaid program.     

Argatroban use in heparin-induced thrombocytopenia

Background: Heparin-induced thrombocytopenia (HIT) is a serious, life-threatening complication which occurs in 1 – 3% of patients receiving heparin. Patients with untreated HIT have an up to 50% risk of developing life- and limb-threatening thromboembolic complications. Treatment is based upon clinical suspicion, stopping heparin therapy and initiation of anticoagulation with a rapidly acting alternative non-heparin anticoagulant, such as argatroban – a hepatically excreted direct thrombin inhibitor which is effective in the treatment of HIT. Objective: To summarize the pharmacological and clinical data, and discuss the impact of argatroban in the current treatment of HIT. Methods: A literature search was performed with the aid of Pubmed and Google. Search parameters of ‘argatroban’, ‘heparin-induced thrombocytopenia’ and ‘treatment’ were input into both search engines. Conclusion: Argatroban is a safe and effective treatment for HIT. In patients taking other hepatically cleared medications, lower initial doses may have to be used to avoid over-anticoagulation.     

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。     

Periprocedural bridging therapy in patients receiving chronic oral anticoagulation therapy

ABSTRACT

Background: In patients receiving chronic oral anticoagulation with vitamin K antagonists (VKAs) it may be necessary to temporarily discontinue VKA therapy to allow surgery or other invasive procedures to be performed, as maintaining treatment may increase the risk of bleeding during the procedure. This, however, creates a clinical dilemma, since discontinuing VKAs may place the patient at risk of thromboembolism.

Scope: We undertook a systematic narrative review of patients on chronic oral anticoagulation, requiring a periprocedural bridging therapy with heparin during invasive procedures.

Findings and recommendations: For patients requiring temporary discontinuation of VKA, current guidelines recommend the use of ‘bridging’ therapy with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) in patients considered to be at intermediate-to-high risk of thromboembolism, such as those with prosthetic heart valves or atrial fibrillation. Recent studies show that LMWHs are associated with low rates of thromboembolism and, when compared with UFH, are as effective and safe as UFH when used as periprocedural bridging therapy in such patients. LMWHs also offer advantages such as ease of administration and predictable anticoagulant effects. Moreover, outpatient-based periprocedural bridging therapy with LMWH has been shown to result in significant cost savings compared with in-hospital UFH.

Conclusions: The decision to provide bridging therapy requires careful consideration of the relative risks of thromboembolism and bleeding in each patient. Based upon the studies reviewed we recommend a therapeutic dose of UFH or LMWH for patients at intermediate-to-high thromboembolic risk requiring interruption of VKA, especially for low bleeding risk procedures. We would like to propose upgrading the American College of Chest Physicians (ACCP) guideline recommendations from 2C to 1C. However, there is still a need for a randomized controlled trial on the efficacy and safety of the available bridging strategies, including heparin and placebo comparators, in preventing thromboembolism for specific patients and procedures.     

长期使用华法林抗凝的非瓣膜性房颤患者围手术/操作期使用NOAC桥接的抗凝方案研究

目的：探讨使用非维生素K拮抗剂的口服抗凝药物（NOAC）代替肝素类药物在围手术/操作期患者进行桥接抗凝的可行性。方法：本研究为前瞻性观察研究,2018年8月至2021年5月入选长期使用华法林抗凝的非瓣膜性房颤患者,观察患者在围手术/操作期使用NOAC桥接抗凝后,围手术/操作期以及术后30天内栓塞事件与出血事件的发生率。结果：共入选患者21例,其中4例行肠镜检查,3例行胃镜检查,8例行拔牙操作,3例行眼科相关操作,3例行皮肤科相关操作。患者的平均年龄（70.8±8.5）岁,女性有9例,平均CHA2DS2-VASc评分（3.0±1.0）分,平均HAS-BLED评分（1.4±0.7）分。21例术后30天均未出现出血事件与栓塞事件。结论：对于非瓣膜性房颤患者,采取NOAC在围手术/操作期进行桥接抗凝,具有一定的可行性。     

Anticoagulant failure in coagulopathic patients: PTT confounding and other pitfalls

Introduction: Devastating thromboses can complicate heparin-induced thrombocytopenia (HIT) and disseminated intravascular coagulation (DIC). In these disorders, acquired abnormalities of the partial thromboplastin time (PTT) and international normalized ratio (INR) can confound monitoring of PTT- and INR-adjusted anticoagulant therapies, contributing to treatment failure.

Areas covered: Illustrative patient cases of anticoagulant failure due to PTT and INR confounding are discussed. Four different scenarios of thrombosis progression associated with inappropriate anticoagulant interruption/underdosing, contributing to ischemic limb necrosis, are presented: i) PTT confounding of heparin therapy of warfarin-associated microthrombosis complicating cancer hypercoagulability; ii) PTT confounding of direct thrombin inhibitor (DTI) therapy complicating HIT-associated DIC; iii) INR confounding during argatroban–warfarin overlap of HIT-associated deep-vein thrombosis; and iv) PTT confounding of anticoagulant therapy during acute DIC/hepatic necrosis–ischemic limb necrosis syndrome.

Expert opinion: Abnormal coagulation test results at pre-treatment baseline can provide an important clue regarding the risk of subsequent anticoagulant failure due to PTT or INR confounding. Greater awareness of the potential for anticoagulant failure due to PTT and INR confounding could assist clinicians in management of prothrombotic coagulopathies, for example, by choosing alternative anticoagulants (e.g., fondaparinux, danaparoid) that are not monitored by global coagulation assays, or by obtaining specific drug levels (anti-factor Xa levels, DTI levels).     

Use of newer anticoagulants in patients with chronic kidney disease.

PURPOSE: The current indications, dosing, and practical considerations for use of newer anticoagulants in patients with various degrees of renal impairment who do not require dialysis are reviewed. SUMMARY: Kidney function should generally be evaluated in all patients commencing anticoagulant therapy. As in the general population, hospitalized patients with impaired renal function most often have impairment that is mild to moderate in severity. Drug dosing in patients with chronic kidney disease may require that adjustment be made to the usual loading or maintenance dose of a drug. Newer anticoagulants with labeling approved by the Food and Drug Administration for venous thromboembolism (VTE) prophylaxis, treatment, or both include the low-molecular-weight heparins (LMWHs) and the factor Xa inhibitor fondaparinux. Some LMWHs are also indicated for the management of patients with acute coronary syndrome (ACS). All of the newer anticoagulants currently available for the management of VTE and ACS have approved labeling for use in patients with mild-to-moderate renal impairment. Currently available LMWHs, factor Xa inhibitors, and direct thrombin inhibitors (excluding argatroban) are eliminated primarily by the kidneys, so dosing in patients with severe renal impairment may require cautious dosage reduction or increased monitoring for bleeding and thromboembolic complications or both. Unfractionated heparin is the preferred anticoagulant for use in most of these patients. CONCLUSION: Newer anticoagulants should be used with caution in patients with mild-to-moderate renal impairment. Unfractionated heparin remains the preferred anticoagulant in most patients with severe renal impairment even though its use is associated with increased bleeding in this population. Dosing of newer anticoagulants, except argatroban, requires cautious dosage reduction and increased monitoring for complications.     

高出血风险患者连续性肾脏替代治疗期间采用阿加曲班和枸橼酸钠抗凝治疗的对比研究

目的 评估小剂量阿加曲班与枸橼酸钠在高出血风险患者连续性肾脏替代治疗(continuous renal replacement therapy,CRRT)中的抗凝效果及安全性。方法 前瞻性收集125例患者分为枸橼酸钠组(n=53)和阿加曲班组(n=72)。比较2组CRRT滤器寿命、凝血功能指标、滤器及管路凝血事件、血栓事件、出血事件、CRRT参数及临床指标情况。结果 阿加曲班组治疗后的凝血酶原时间、国际标准化比值、活化部分凝血活酶时间与枸橼酸钠组相比均有延长(P<0.05)。2组的凝血事件差异无统计学意义，但是枸橼酸钠组的静脉壶无凝血比例高于阿加曲班组(P<0.05)，滤器寿命也更长(P<0.05)。枸橼酸钠组总不良反应发生率高于阿加曲班组(P=0.001)。2组发生滤器凝血事件的血流量和超滤率均低于未发生滤器凝血事件的血流量和超滤率(P<0.05)。结论 枸橼酸钠在CRRT中的抗凝效果更具优势，但阿加曲班安全性更好，对于低血流量和低超滤率的CRRT宜增加阿加曲班抗凝剂量。     

高危消化内镜干预对抗凝治疗患者的临床安全性研究

目的探讨高危消化内镜干预对服用华法林患者的临床安全性。方法入选服用华法林同时需行高危内镜操作的患者148例,术后分为早期抗凝组73人（术后8h内恢复抗凝治疗）和延迟抗凝组75人（术后第3 d恢复抗凝治疗）。比较两组患者出血发生率和血栓发生率。结果两组患者出血事件发生率差异无统计学意义（9.59%vs.4.00%,P=0.304）,早期恢复抗凝治疗出血风险的OR值为1.28,延迟抗凝组血栓事件发生率较高（12.00%vs.2.74%,P=0.031）,延迟抗凝血栓风险的OR值为3.83。结论对于服用华法林的患者,高危消化内镜术后8 h内恢复抗凝治疗可以降低血栓发生风险,而出血风险增加相对不明显。