阿加曲班序贯于巴曲酶治疗急性缺血性卒中的临床观察

目的:评价阿加曲班注射液序贯于巴曲酶治疗急性脑梗死的有效性和安全性.方法:急性脑梗死患者72例随机分为巴曲酶组及联合治疗组,各36例;巴曲酶组,在常规治疗基础上增加巴曲酶治疗;联合治疗组在常规治疗基础上给予阿加曲班序贯于巴曲酶治疗.分别于治疗前、治疗后3、7、10、14及21 d测定各组纤维蛋白原(FIB)、凝血酶原时...     

阿加曲班和利伐沙班在急性静脉血栓中的临床疗效比较

目的 比较阿加曲班和利伐沙班在急性静脉血栓形成患者中的疗效和不良反应.方法 采用回顾性研究方法分析武汉协和医院2010年6月至2012年6月收治的静脉血栓栓塞症患者254例.将患者分为对照组(98例)、阿加曲班组(101例)和利伐沙班组(55例).对照组给予普通肝素1.25×104U加生理盐水配制成48 mL,2mL/h,24h静脉持续泵入,疗程7d;阿加曲班组患者开始2d,阿加曲班注射液40 mg以适当生理盐水配制成96 mL,以4mL/h,24 h静脉持续泵入,后5d,阿加曲班注射液20 mg以适当生理盐水配制成48 mL,2 mL/h,24 h静脉持续泵入,疗程7d;利伐沙班组予以利伐沙班片10 mg/d,口服,疗程7d.每日测量患者双下肢周径,监测凝血功能,血、尿常规及大便潜血等实验室指标,另外检测用药前和用药第7日的D-二聚体水平并观察患者有无出血倾向及出血.所有患者7d后改为口服华法林治疗3～6月,检测INR值,调整华法林剂量,维持INR值于2.0～3.0.结果 经过7d治疗后,阿加曲班组下肢肿胀缓解率为95％,利伐沙班组为89％,对照组为96％,3组比较无差异.用药7d后,3组D-二聚体水平变化差异无统计学意义.阿加曲班组、利伐沙班组出血不良反应发生率低于对照组(P＜0.05).结论 阿加曲班和利伐沙班作为新型抗凝药物,其临床疗效与传统抗凝药物普通肝素相比无明显差异,但阿加曲班相比于普通肝素出血等不良反应较少,同时,不会引起患者血小板减少.     

Treatment of Patients with a History of Heparin-Induced Thrombocytopenia and Anti-Lepirudin Antibodies with Argatroban

Patients with heparin-induced thrombocytopenia (HIT) type II require anticoagulation with non-heparin immediate acting anticoagulants. Danaparoid may cross react with HIT-antibodies and lepirudin may generate anti-lepirudin antibodies influencing anticoagulation. We hypothesised, that the synthetic small molecular thrombin inhibitor argatroban does not induce immunoglobulins reacting towards lepirudin in patients with anti-lepirudin antibodies in the history and that titration of the anticoagulation may be easier with argatroban. We report on the treatment of four patients of a study, which was terminated prematurely due to official warnings for a repeated use of lepirudin. Two patients each received argatroban and lepirudin intravenously. A blinded assessor adjusted the doses of the anticoagulants to 1.5–3.0 fold prolongation of the aPTT. Ecarin clotting time (ECT), concentrations of lepirudin (ELISA) and of argatroban (gaschromatoraphy with mass spectrometry,) and the generation of lepirudin antibodies (ELISA) were measured. APTT-adjusted dosages for argatroban was 2.0–2.6 μg/kg⋅ min and for lepirudin 48–149 μ g/kg⋅ h. ECT was prolonged 2.1 to 4.5-fold with lepirudin and 4 to 7-fold with argatroban. The concentration of lepirudin ranged between 750 and 1500 ng/ml and of argatroban between 400 and 1100 ng/ml. Patients on argatroban did not generate immunoglobulin IgG reacting towards lepirudin in contrast to both patients on lepirudin who developed anti-lepirudin antibodies. Both treatments were well tolerated. Despite the low number of patients argatroban seems to lead to a more stable anticoagulant response than lepirudin resulting in a lower variability of the dosage for prophylaxis or treatment of thromboembolism of patients with a history of HIT and lepirudin antibodies. An erratum to this article can be found at .     

3种改善血液循环药物联合基础治疗用于急性脑梗死的网状Meta分析及药物经济学评价

目的 通过评价3种改善血液循环类药物（阿加曲班注射液、丁苯酞注射液和尤瑞克林注射液）分别联合基础治疗（抗血小板+调脂、抗血小板+调脂+阿替普酶）用于治疗急性脑梗死的有效性、安全性及经济性,为相关决策提供参考。方法 检索中国知网数据库、重庆维普中文科技期刊数据库、万方数据库、PubMed、Web of Science等数据库并搜集相关的临床试验,采用Stata 14.1软件,进行基于NIHSS有效率、不良反应发生率的网状Meta分析,以评价有效性和安全性;采用最小成本分析法和成本-效果分析法进行经济性评价。结果 共纳入32篇文献,涉及3 071例患者。有效性和安全性网状Meta分析结果均显示,各干预措施的差异无统计学意义。但从严重不良反应发生情况来看,阿加曲班组的严重不良反应发生率相对最低,安全性相对最好,其次依次为丁苯酞组和尤瑞克林组。经济性评价结果显示,阿加曲班组的经济性相对最佳。结论 与丁苯酞组和尤瑞克林组相比,阿加曲班联合基础治疗的有效性和安全性良好、严重不良反应最少,且经济性最佳。     

阿加曲班药理作用和临床应用研究进展

阿加曲班为一种直接凝血酶抑制剂,通过抑制纤维蛋白形成,血小板聚集,凝血因子Ⅴ、Ⅷ和Ⅻ和蛋白C的活性,发挥其抗凝血作用,不但灭活液相凝血酶,还能够灭活与纤维蛋白血栓结合的凝血酶。阿加曲班对凝血酶具有高度亲和性,具有无抗原性、构效关系明确、半衰期短、临床使用安全等特点。可用于急性缺血性脑卒中、经皮冠状动脉介入术、慢性动脉闭塞症和肝素诱导血小板减少症等的治疗。阿加曲班还通过对凝血酶的抑制,发挥抗炎、抑制血栓形成和抑制肿瘤转移等的作用。此外,阿加曲班还有非凝血酶抑制作用,如扩张血管和改善微循环等,以及潜在的抗病毒活性。对阿加曲班的药理作用、临床应用研究进展以及临床应用需要注意的问题等方面进行综述,为阿加曲班临床更高效合理使用提供参考。     

阿加曲班对急性脑梗死患者血清白细胞介素8水平的影响

目的:观察阿加曲班对急性脑梗死(ACI)患者血清白细胞介素8(IL-8)水平的影响。方法:开放随机对照研究,65例患者按1∶1∶1方法随机分成3组:对照组,治疗组A和治疗组B,3组均采用基础治疗,治疗组在基础治疗外合并应用阿加曲班,治疗组A阿加曲班60 mg·d-1溶解于溶液中静脉滴注,连续48 h治疗,治疗组B阿加曲班60 mg·d-1溶解于溶液中静脉滴注,连续48 h治疗后,随后阿加曲班10 mg溶解于溶液中静脉滴注,bid,连续5 d。入院后即刻(d0),第1,2,3,4,6,9,12天及入院后第4周,各抽空腹静脉血2 mL检测IL-8水平的变化。结果:阿加曲班可明显降低血清IL-8的水平(P<0.05),但比较应用阿加曲班2 d 60 mg·d-1和持续阿加曲班48 h后随即给予每次10 mg,bid,连续5 d,2组IL-8的变化曲线无差异(P>0.05)。结论:早期48 h应用大剂量(60 mg·d-1)阿加曲班可明显降低血清IL-8水平,但持续应用至1周比仅使用48 h不能更加降低血清IL-8水平。     

Results of a consensus meeting on the use of argatroban in patients with heparin-induced thrombocytopenia requiring antithrombotic therapy - a European Perspective

Argatroban has been introduced as an alternative parenteral anticoagulant for HIT-patients in several European countries in 2005. In 2009 a panel of experts discussed their clinical experience with argatroban balancing risks and benefits of argatroban treatment in managing the highly procoagulant status of HIT-patients. This article summarizes the main conclusions of this round table discussion. An ongoing issue is the appropriate dosing of argatroban in special patient groups. Therefore, dosing recommendations for different HIT-patient groups (ICU patients; non-ICU patients, paediatric patients, and for patients undergoing renal replacement therapies) are summarized in this consensus statement. Because of the strong correlation between argatroban dosing requirements and scores used to characterize the severity of illness (APACHE; SAPS, SOFA) suitable dosing nomograms are given.This consensus statement contributes to clinically relevant information on the appropriate use and monitoring of argatroban based on the current literature, and provides additional information from clinical experience. As the two other approved drugs for HIT, danaparoid and lepirudin are either currently not available due to manufacturing problems (danaparoid) or will be withdrawn from the market in 2012 (lepirudin), this report should guide physicians who have limited experience with argatroban how to use this drug safely in patients with HIT.     

A Synopsis of the Clinical Uses of Argatroban

Argatroban, a direct thrombin inhibitor, has been used in Japan since the early 1980's and was recently approved for use in the United States for patients with heparin-induced thrombocytopenia. However, its use has been studied in other clinical settings including, myocardial infarction, percutaneous coronary intervention and cerebral thrombosis. The doses used in the different clinical situations vary, but argatroban offers the advantage of not requiring renal adjustment. Because of its small molecular weight, argatroban has the ability to inhibit both clot bound and soluble thrombin. This paper provides a comprehensive review of both indicated and off label uses of argatroban. Pharmacology, pharmacokinetics, adverse events and drug interactions with argatroban are also discussed.