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体外评估纤维蛋白原、重组因子 VIIa 和因子 XIII 对创伤诱导性凝血病的影响。

In-vitro assessment of the effects of fibrinogen, recombinant factor VIIa and factor XIII on trauma-induced coagulopathy.

机构信息

Department of Pathophysiology, Sechenov First Moscow State Medical University, Moscow, Russia.

Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer, Israel.

出版信息

Blood Coagul Fibrinolysis. 2020 Jun;31(4):253-257. doi: 10.1097/MBC.0000000000000910.

Abstract

: Trauma-induced coagulopathy (TIC) occurs commonly as a second event following severe injury. We evaluated the effects of fibrinogen, recombinant factor VIIa and factor XIII on blood clotting and fibrinolysis in an in-vitro TIC model. The TIC model included hemodilution, hyperfibrinolysis, acidosis and hypothermia. The extent of clot formation and fibrinolysis was evaluated using rotational thromboelastometry. Clot strength was increased following spiking the TIC blood with either 1.0 mg/ml fibrinogen, 3.0 μg/ml recombinant factor VIIa or 2.0 IU/ml factor XIII. Maximal effect was achieved by all agents in combination approximating the extent of clot formation to those in normal blood. Fibrinolysis was inhibited by factor XIII, while the reduction was stronger using all agents together. When each of the agents used in two times lower concentrations, clot strength was near to threshold. Fibrinogen and factor XIII but not factor VIIa exerted stimulation of clot strength, whereas synergistic effect of fibrinogen and factor XIII was observed. Maximal effect was achieved combining all agents. The antifibrinolytic effect was observed only by co-administration of fibrinogen, factor XIII and factor VIIa. On the basis of our study, we suggest that stimulation of clot formation and inhibition of fibrinolysis may be achieved by combination of FG, rFVIIa an FXIII using each of them at minimal effective concentration. Taken into consideration, multifactorial TIC pathogenesis, this approach may be preferable for improving coagulopathy than separate blood spiking with the essayed factors at high concentrations.

摘要

创伤诱导的凝血病(TIC)作为严重损伤后的第二个事件经常发生。我们评估了纤维蛋白原、重组因子 VIIa 和因子 XIII 对体外 TIC 模型中血液凝固和纤维蛋白溶解的影响。TIC 模型包括血液稀释、过度纤维蛋白溶解、酸中毒和低体温。使用旋转血栓弹性测定法评估血栓形成和纤维蛋白溶解的程度。在 TIC 血液中添加 1.0mg/ml 纤维蛋白原、3.0μg/ml 重组因子 VIIa 或 2.0IU/ml 因子 XIII,均可增加血栓形成强度。所有药物联合使用,可达到接近正常血液的血栓形成程度,从而达到最大效果。因子 XIII 抑制纤维蛋白溶解,而所有药物联合使用时抑制作用更强。当每种药物的浓度降低两倍时,血栓形成强度接近阈值。纤维蛋白原和因子 XIII 但不是因子 VIIa 发挥增强血栓形成强度的作用,而纤维蛋白原和因子 XIII 存在协同作用。联合使用所有药物可达到最大效果。只有联合使用纤维蛋白原、因子 XIII 和因子 VIIa 才能观察到抗纤维蛋白溶解作用。基于我们的研究,我们建议通过将 FG、rFVIIa 和 FXIII 以最小有效浓度联合使用,可实现血栓形成的刺激和纤维蛋白溶解的抑制。考虑到 TIC 的多因素发病机制,与单独使用高浓度的这些因子进行血液刺激相比,这种方法可能更有利于改善凝血病。

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