Treschan Tanja A, Schaefer Maximilian S, Geib Johann, Bahlmann Astrid, Brezina Tobias, Werner Patrick, Golla Elisabeth, Greinacher Andreas, Pannen Benedikt, Kindgen-Milles Detlef, Kienbaum Peter, Beiderlinden Martin
Crit Care. 2014 Oct 25;18(5):588. doi: 10.1186/s13054-014-0588-8.
Critically ill patients often require renal replacement therapy accompanied by thrombocytopenia. Thrombocytopenia during heparin anticoagulation may be due to heparin-induced thrombocytopenia with need for alternative anticoagulation. Therefore, we compared argatroban and lepirudin in critically ill surgical patients.
Following institutional review board approval and written informed consent, critically ill surgical patients more than or equal to 18 years with suspected heparin-induced thrombocytopenia, were randomly assigned to receive double-blind argatroban or lepirudin anticoagulation targeting an activated Partial Thromboplastin Time (aPTT) of 1.5 to 2 times baseline. In patients requiring continuous renal replacement therapy we compared the life-time of hemodialysis filters. We evaluated in all patients the incidence of bleeding and thrombembolic events.
We identified 66 patients with suspected heparin-induced thrombocytopenia, including 28 requiring renal replacement therapy. Mean filter lifetimes did not differ between groups (argatroban 32 ± 25 hours (n = 12) versus lepirudin 27 ± 21 hours (n = 16), mean difference 5 hours, 95% CI -13 to 23, P = 0.227). Among all 66 patients, relevant bleeding occurred in four argatroban- versus eleven lepirudin-patients (OR 3.9, 95% CI 1.1 to 14.0, P = 0.040). In the argatroban-group, three thromboembolic events occurred compared to two in the lepirudin group (OR 0.7, 95% CI 0.1 to 4.4, P = 0.639). The incidence of confirmed heparin-induced thrombocytopenia was 23% (n = 15) in our study population.
This first randomized controlled double-blind trial comparing two direct thrombin inhibitors showed comparable effectiveness for renal replacement therapy, but suggests fewer bleeds in surgical patients with argatroban anticoagulation.
Clinical Trials.gov NCT00798525. Registered 25 November 2008.
重症患者常需进行肾脏替代治疗，且伴有血小板减少症。肝素抗凝期间的血小板减少症可能是由于肝素诱导的血小板减少症，需要采用替代抗凝方法。因此，我们比较了阿加曲班和比伐卢定在重症外科患者中的应用。
经机构审查委员会批准并获得书面知情同意后，将18岁及以上疑似肝素诱导的血小板减少症的重症外科患者随机分配，接受双盲阿加曲班或比伐卢定抗凝治疗，目标活化部分凝血活酶时间（aPTT）为基线的1.5至2倍。对于需要持续肾脏替代治疗的患者，我们比较了血液透析滤器的使用寿命。我们评估了所有患者出血和血栓栓塞事件的发生率。
我们确定了66例疑似肝素诱导的血小板减少症患者，其中28例需要肾脏替代治疗。两组之间的平均滤器使用寿命无差异（阿加曲班组32±25小时（n = 12），比伐卢定组27±21小时（n = 16），平均差异5小时，95%CI -13至23，P = 0.227）。在所有66例患者中，4例接受阿加曲班治疗的患者与11例接受比伐卢定治疗的患者发生了相关出血（OR 3.9，95%CI 1.1至14.0，P = 0.040）。在阿加曲班组，发生了3例血栓栓塞事件，而比伐卢定组为2例（OR 0.7，95%CI 0.1至4.4，P = 0.639）。在我们的研究人群中，确诊的肝素诱导的血小板减少症发生率为23%（n = 15）。
这项比较两种直接凝血酶抑制剂的首次随机对照双盲试验表明，在肾脏替代治疗方面两者有效性相当，但提示阿加曲班抗凝的外科患者出血较少。
ClinicalTrials.gov NCT00798525。于2008年11月25日注册。
