逆转利伐沙班抗凝作用作为多模式止血干预的一部分在多发伤动物模型中的应用。
Reversing Rivaroxaban Anticoagulation as Part of a Multimodal Hemostatic Intervention in a Polytrauma Animal Model.
机构信息
From the Departments of Anesthesiology, RWTH Aachen University Hospital, Aachen, Germany.
Pathology, RWTH Aachen University Hospital, Aachen, Germany.
出版信息
Anesthesiology. 2021 Oct 1;135(4):673-685. doi: 10.1097/ALN.0000000000003899.
BACKGROUND
Life-threatening bleeding requires prompt reversal of the anticoagulant effects of factor Xa inhibitors. This study investigated the effectiveness of four-factor prothrombin complex concentrate in treating trauma-related hemorrhage with rivaroxaban-anticoagulation in a pig polytrauma model. This study also tested the hypothesis that the combined use of a low dose of prothrombin complex concentrate plus tranexamic acid and fibrinogen concentrate could improve its subtherapeutic effects.
METHODS
Trauma (blunt liver injury and bilateral femur fractures) was induced in 48 anesthetized male pigs after 30 min of rivaroxaban infusion (1 mg/kg). Animals in the first part of the study received prothrombin complex concentrate (12.5, 25, and 50 U/kg). In the second part, animals were treated with 12.5 U/kg prothrombin complex concentrate plus tranexamic acid or plus tranexamic acid and fibrinogen concentrate. The primary endpoint was total blood loss postinjury. The secondary endpoints (panel of coagulation parameters and thrombin generation) were monitored for 240 min posttrauma or until death.
RESULTS
The first part of the study showed that blood loss was significantly lower in the 25 U/kg prothrombin complex concentrate (1,541 ± 269 ml) and 50 U/kg prothrombin complex concentrate (1,464 ± 108 ml) compared with control (3,313 ± 634 ml), and 12.5 U/kg prothrombin complex concentrate (2,671 ± 334 ml, all P < 0.0001). In the second part of the study, blood loss was significantly less in the 12.5 U/kg prothrombin complex concentrate plus tranexamic acid and fibrinogen concentrate (1,836 ± 556 ml, P < 0.001) compared with 12.5 U/kg prothrombin complex concentrate plus tranexamic acid (2,910 ± 856 ml), and there were no early deaths in the 25 U/kg prothrombin complex concentrate, 50 U/kg prothrombin complex concentrate, and 12.5 U/kg prothrombin complex concentrate plus tranexamic acid and fibrinogen concentrate groups. Histopathologic analyses postmortem showed no adverse events.
CONCLUSIONS
Prothrombin complex concentrate effectively reduced blood loss, restored hemostasis, and balanced thrombin generation. A multimodal hemostatic approach using tranexamic acid plus fibrinogen concentrate enhanced the effect of low doses of prothrombin complex concentrate, potentially reducing the prothrombin complex concentrate doses required for effective bleeding control.
背景
危及生命的出血需要迅速逆转因子 Xa 抑制剂的抗凝作用。本研究在猪多发伤模型中，研究了四种因子凝血酶原复合物浓缩物治疗利伐沙班抗凝相关出血的疗效。本研究还检验了一种假设，即联合使用低剂量凝血酶原复合物浓缩物加氨甲环酸和纤维蛋白原浓缩物可提高其亚治疗效果。
方法
在利伐沙班输注 30 分钟后，对 48 只麻醉雄性猪进行创伤（钝性肝损伤和双侧股骨骨折），以诱导创伤。研究的第一部分，猪接受凝血酶原复合物浓缩物（12.5、25 和 50 U/kg）。在第二部分，猪接受 12.5 U/kg 凝血酶原复合物浓缩物加氨甲环酸或加氨甲环酸和纤维蛋白原浓缩物治疗。主要终点是损伤后总失血量。次要终点（凝血参数和凝血酶生成面板）在创伤后 240 分钟或直至死亡时监测。
结果
研究的第一部分表明，与对照组（3313 ± 634 ml）相比，25 U/kg 凝血酶原复合物浓缩物（1464 ± 108 ml）和 50 U/kg 凝血酶原复合物浓缩物（1464 ± 108 ml）的失血明显减少，12.5 U/kg 凝血酶原复合物浓缩物（2671 ± 334 ml，均 P < 0.0001）。在研究的第二部分，与 12.5 U/kg 凝血酶原复合物浓缩物加氨甲环酸相比，12.5 U/kg 凝血酶原复合物浓缩物加氨甲环酸和纤维蛋白原浓缩物（1836 ± 556 ml，P < 0.001）的失血明显减少，且 25 U/kg 凝血酶原复合物浓缩物、50 U/kg 凝血酶原复合物浓缩物和 12.5 U/kg 凝血酶原复合物浓缩物加氨甲环酸和纤维蛋白原浓缩物组均无早期死亡。死后组织病理学分析显示无不良事件。
结论
凝血酶原复合物浓缩物有效减少失血，恢复止血，平衡凝血酶生成。使用氨甲环酸加纤维蛋白原浓缩物的多模式止血方法增强了低剂量凝血酶原复合物浓缩物的效果，可能减少有效控制出血所需的凝血酶原复合物浓缩物剂量。
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