Oliver Grottke, MD PhD, Department of Anaesthesiology, RWTH Aachen University Hospital, Pauwelsstrasse 30; 52074 Aachen, Germany, Tel.: +49 241 8080972, Fax: +49 241 8082406, E-mail:
Thromb Haemost. 2016 Jan;115(2):271-84. doi: 10.1160/TH15-03-0266. Epub 2015 Sep 3.
Clinical use of non-vitamin K antagonist oral anticoagulants is increasingly well established. However, specific agents for reversal of these drugs are not currently available. It was to objective of this study to investigate the impact of activated prothrombin complex concentrate (aPCC) on the anticoagulant effects of dabigatran in a randomised, controlled, porcine trauma model. Twenty-one pigs received oral and intravenous dabigatran, resulting in supratherapeutic plasma concentrations. Twelve minutes after injury (standardised bilateral femur fractures and blunt liver injury), animals (n=7/group) received 25 or 50 U/kg aPCC (aPCC25 and aPCC50) or placebo (control) and were followed for 5 hours. The primary endpoint was total volume of blood loss (BL). Haemodynamic and coagulation variables (prothrombin time [PT], activated partial thromboplastin time, diluted thrombin time, thrombin-antithrombin complexes, thromboelastometry, thrombin generation and D-dimers) were measured. Twelve minutes post-injury, BL was similar between groups. Compared with control (total BL: 3807 ± 570 ml) and aPCC25 (3690 ± 454 ml; p=0.77 vs control), a significant reduction in total BL (1639 ± 276 ml; p< 0.0001) and improved survival (p< 0.05) was observed with aPCC50. Dabigatran's anticoagulant effects were effectively treated in the aPCC50 group, as measured by several parameters including EXTEM clotting time (CT) and PT. In contrast, with aPCC25, laboratory values were initially corrected but subsequently deteriorated due to ongoing blood loss. Thromboembolic or bleeding effects were not detected. In conclusion, blood loss following trauma in dabigatran-anticoagulated pigs was successfully reduced by 50 U/kg aPCC. Optimal methodology for measuring amelioration of dabigatran anticoagulation by aPCC is yet to be determined.
非维生素 K 拮抗剂口服抗凝剂的临床应用已得到充分证实。然而，目前尚无这些药物逆转的特定药物。本研究旨在探讨随机对照猪创伤模型中激活的凝血酶原复合物浓缩物（aPCC）对达比加群抗凝作用的影响。21 头猪口服和静脉注射达比加群，使血浆浓度达到治疗窗以上。损伤后 12 分钟（双侧股骨骨折和钝性肝损伤标准化），动物（n=7/组）给予 25 或 50 U/kg aPCC（aPCC25 和 aPCC50）或安慰剂（对照组），并随访 5 小时。主要终点是总失血量（BL）。测量血流动力学和凝血变量（凝血酶原时间[PT]、活化部分凝血活酶时间、稀释凝血酶时间、凝血酶-抗凝血酶复合物、血栓弹力图、血栓生成和 D-二聚体）。损伤后 12 分钟，各组间 BL 相似。与对照组（总 BL：3807±570ml）和 aPCC25（3690±454ml；p=0.77 与对照组）相比，aPCC50 可显著减少总 BL（1639±276ml；p<0.0001）并提高存活率（p<0.05）。aPCC50 可有效治疗达比加群抗凝作用，这可通过 EXTEM 凝血时间（CT）和 PT 等多个参数来衡量。相比之下，用 aPCC25 时，实验室值最初得到纠正，但随后因持续失血而恶化。未发现血栓栓塞或出血作用。总之，达比加群抗凝的猪创伤后失血可通过 50 U/kg aPCC 成功减少。用于测量 aPCC 改善达比加群抗凝作用的最佳方法仍有待确定。
