Department of Medicine III, Martin-Luther-University, Ernst-Grube-Str. 40, 06097 Halle, Germany.
Thromb Haemost. 2010 Apr;103(4):808-14. doi: 10.1160/TH09-07-0456. Epub 2010 Feb 19.
The direct thrombin inhibitor argatroban offers some significant advantages over unfractionated heparin (UFH) and is recommended as an alternative anticoagulant during percutaneous coronary interventions (PCI). The impact of argatroban on cardiac catheter thrombosis--a severe potential complication of PCI--has not been systematically studied yet. The aim of the present study was to test in vitro the hypothesis that argatroban is equivalent to the more established anticoagulants UFH and enoxaparin in preventing catheter thrombus formation. Blood pretreated with the anticoagulants of interest was continuously circulated through a guiding catheter by using a roller pump for a maximum experimental period of 60 minutes. In an alternate model, coagulation was mechanically induced by a magnetic stirrer. Coagulation parameters, overall thrombus weight and electron microscopic features (deposits of platelets and fibrin on the catheter surface) were quantified as endpoints. Argatroban (administered as bolus or continuous infusion), UFH (bolus), and enoxaparin (bolus) significantly reduced catheter thrombus formation compared to untreated controls. Here, neither overall thrombus weight nor platelet/fibrin deposition was different among the specific anticoagulants. Declining ACT (activated clotting time) levels--which were found in the argatroban bolus group--could be prevented by continuous infusion. In magnetic stirrer-induced coagulation, thrombus weight was lower following bolus treatment with UFH and enoxaparin compared to argatroban. These data suggest that the potential for argatroban in preventing catheter thrombosis is comparable to that of UFH and enoxaparin. However, the anticoagulatory efficacy varied, depending on the model of coagulation activation, which demonstrates the necessity for specific testing.
直接凝血酶抑制剂阿加曲班相对于未分级肝素 (UFH) 具有一些显著优势，并且被推荐作为经皮冠状动脉介入治疗 (PCI) 期间的替代抗凝剂。阿加曲班对经皮冠状动脉介入治疗血栓形成的影响——这是一种严重的潜在并发症——尚未得到系统研究。本研究的目的是在体外测试阿加曲班在预防导管血栓形成方面等效于更成熟的抗凝剂 UFH 和依诺肝素的假设。用滚轴泵将用感兴趣的抗凝剂预处理的血液连续循环通过引导导管，最长实验时间为 60 分钟。在另一个模型中，通过搅拌器机械诱导凝血。将凝血参数、总血栓重量和电子显微镜特征（导管表面血小板和纤维蛋白的沉积）作为终点进行量化。与未处理的对照组相比，阿加曲班（推注或连续输注）、UFH（推注）和依诺肝素（推注）显著减少了导管血栓形成。在这里，特定抗凝剂之间的总血栓重量或血小板/纤维蛋白沉积没有差异。在阿加曲班推注组中发现的下降的 ACT（活化凝血时间）水平可以通过连续输注来预防。在搅拌器诱导的凝血中，与阿加曲班相比，UFH 和依诺肝素的推注治疗后血栓重量较低。这些数据表明，阿加曲班预防导管血栓形成的潜力与 UFH 和依诺肝素相当。然而，抗凝效果因凝血激活模型而异，这表明需要进行特定的测试。
