Background:In light of decreased intracranial hemorrhage with direct oral anticoagulants and concerns about their safety in continuous flow left ventricular assist devices, we conducted an ex vivo study of thrombus formation using multiple anticoagulation agents.Methods:A continuous flow left ventricular assist device (HeartWare ventricular assist device) hemocompatibility loop was run using human blood under 7 conditions: control (no anticoagulation or antiplatelet); in vitro addition of aspirin; in vitro addition of apixaban at low dose (equivalent 2.5 mg twice daily); addition of apixaban at high dose (equivalent 5 mg twice daily); patients on warfarin; patients on apixaban (5 mg twice daily); and patients on dabigatran (150 mg twice daily). The primary outcome was time to formation of intrapump thrombosis. Secondary outcomes were reduction in clotting times over 1 hour, hemolysis, reduced platelet aggregation, and von Willebrand activity.Results:Twenty-one runs were completed. Times to thrombosis in median (interquartile range) were control, 131 (127–134.5); in vitro aspirin, 124 (114.5–137); and patients on dabigatran, 131 (130.5–135.5) minutes, respectively. Times in patients on warfarin were, 137 (136.5–143.5); in vitro low-dose apixaban, 141 (138.5–142); and patients on apixaban, 140 (138–142.5) minutes, respectively. No thrombus formed in the in vitro high-dose apixaban group. There were no significant differences between the individual groups. When all apixaban groups were compared with nonapixaban groups, the time to thrombosis formation was significantly longer, 143 (137–150) versus 133.5 (128.5–140) minutes, P=0.02. There were similar changes in lactate dehydrogenase levels and other secondary end points.Conclusions:In an in vitro study of anticoagulation using human blood in a mock loop with a HeartWare HVAD, we demonstrated similar thrombosis times for apixaban and warfarin. Time to clotting was longer in the combined apixaban groups compared with combined other groups, but thrombosis times between individual groups were not significantly different.

中文翻译：

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不同口服抗凝剂方案对 HeartWare 心室辅助装置中泵血栓形成的体外评估

背景：鉴于直接口服抗凝剂可减少颅内出血以及对其在连续流左心室辅助装置中的安全性的担忧，我们使用多种抗凝剂对血栓形成进行了体外研究。方法：连续流左心室辅助装置（HeartWare心室辅助装置）血液相容性循环在 7 种条件下使用人血运行：对照（无抗凝或抗血小板）；体外添加阿司匹林；体外添加低剂量阿哌沙班（相当于每天两次 2.5 毫克）；添加高剂量阿哌沙班（相当于每天两次 5 毫克）；服用华法林的患者；服用阿哌沙班的患者（每天两次，每次 5 毫克）；和服用达比加群（150 毫克，每天两次）的患者。主要结果是形成泵内血栓形成的时间。次要结果是 1 小时内凝血时间减少、溶血、血小板聚集减少和血管性血友病活动。结果：完成了 21 次运行。中位数（四分位距）血栓形成时间为控制值，131 (127–134.5)；体外阿司匹林，124 (114.5–137)；和达比加群的患者，分别为 131 (130.5–135.5) 分钟。华法林患者的次数为 137 (136.5–143.5)；体外低剂量阿哌沙班，141 (138.5–142)；和服用阿哌沙班的患者，分别为 140 (138–142.5) 分钟。体外高剂量阿哌沙班组未形成血栓。各组之间没有显着差异。当所有阿哌沙班组与非阿哌沙班组进行比较时，血栓形成时间明显更长，分别为 143 (137-150) 分钟和 133.5 (128.5-140) 分钟，溶血、血小板聚集减少和 von Willebrand 活动。结果：完成了 21 次运行。中位数（四分位距）血栓形成时间为控制值，131 (127–134.5)；体外阿司匹林，124 (114.5–137)；和达比加群的患者，分别为 131 (130.5–135.5) 分钟。华法林患者的次数为 137 (136.5–143.5)；体外低剂量阿哌沙班，141 (138.5–142)；和服用阿哌沙班的患者，分别为 140 (138–142.5) 分钟。体外高剂量阿哌沙班组未形成血栓。各组之间没有显着差异。当所有阿哌沙班组与非阿哌沙班组进行比较时，血栓形成时间明显更长，分别为 143 (137-150) 分钟和 133.5 (128.5-140) 分钟，溶血、血小板聚集减少和 von Willebrand 活动。结果：完成了 21 次运行。中位数（四分位距）血栓形成时间为控制值，131 (127–134.5)；体外阿司匹林，124 (114.5–137)；和达比加群的患者，分别为 131 (130.5–135.5) 分钟。华法林患者的次数为 137 (136.5–143.5)；体外低剂量阿哌沙班，141 (138.5–142)；和服用阿哌沙班的患者，分别为 140 (138–142.5) 分钟。体外高剂量阿哌沙班组未形成血栓。各组之间没有显着差异。当所有阿哌沙班组与非阿哌沙班组进行比较时，血栓形成时间明显更长，分别为 143 (137-150) 分钟和 133.5 (128.5-140) 分钟，完成了二十一次运行。中位数（四分位距）血栓形成时间为控制值，131 (127–134.5)；体外阿司匹林，124 (114.5–137)；和达比加群的患者，分别为 131 (130.5–135.5) 分钟。华法林患者的次数为 137 (136.5–143.5)；体外低剂量阿哌沙班，141 (138.5–142)；和服用阿哌沙班的患者，分别为 140 (138–142.5) 分钟。体外高剂量阿哌沙班组未形成血栓。各组之间没有显着差异。当所有阿哌沙班组与非阿哌沙班组进行比较时，血栓形成时间明显更长，分别为 143 (137-150) 分钟和 133.5 (128.5-140) 分钟，完成了二十一次运行。中位数（四分位距）血栓形成时间为控制值，131 (127–134.5)；体外阿司匹林，124 (114.5–137)；和达比加群的患者，分别为 131 (130.5–135.5) 分钟。华法林患者的次数为 137 (136.5–143.5)；体外低剂量阿哌沙班，141 (138.5–142)；和服用阿哌沙班的患者，分别为 140 (138–142.5) 分钟。体外高剂量阿哌沙班组未形成血栓。各组之间没有显着差异。当所有阿哌沙班组与非阿哌沙班组进行比较时，血栓形成时间明显更长，分别为 143 (137-150) 分钟和 133.5 (128.5-140) 分钟，5) 分钟，分别。华法林患者的次数为 137 (136.5–143.5)；体外低剂量阿哌沙班，141 (138.5–142)；和服用阿哌沙班的患者，分别为 140 (138–142.5) 分钟。体外高剂量阿哌沙班组未形成血栓。各组之间没有显着差异。当所有阿哌沙班组与非阿哌沙班组进行比较时，血栓形成时间明显更长，分别为 143 (137-150) 分钟和 133.5 (128.5-140) 分钟，5) 分钟，分别。华法林患者的次数为 137 (136.5–143.5)；体外低剂量阿哌沙班，141 (138.5–142)；和服用阿哌沙班的患者，分别为 140 (138–142.5) 分钟。体外高剂量阿哌沙班组未形成血栓。各组之间没有显着差异。当所有阿哌沙班组与非阿哌沙班组进行比较时，血栓形成时间明显更长，分别为 143 (137-150) 分钟和 133.5 (128.5-140) 分钟，P = 0.02。乳酸脱氢酶水平和其他次要终点也有类似的变化。结论：在具有 HeartWare HVAD 的模拟回路中使用人血进行抗凝的体外研究中，我们证明阿哌沙班和华法林的血栓形成时间相似。与联合其他组相比，联合阿哌沙班组的凝血时间更长，但各组之间的血栓形成时间没有显着差异。