Shenkman Boris, Budnik Ivan, Einav Yulia, Hauschner Hagit, Andrejchin Mykhaylo, Martinowitz Uriel
From the National Hemophilia Center (B.S., U.M.), Sheba Medical Center, Tel-Hashomer, Israel; Department of Pathophysiology (I.B.), Sechenov First Moscow State Medical University, Moscow, Russia; Faculty of Engineering (Y.E.), Holon Institute of Technology, Holon, Israel; Amalia Biron Research Institute of Thrombosis and Hemostasis (H.H.), Chaim Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel; and I. Ya. Horbachevsky Ternopil State Medical University (M.A.), Ternopil, Ukraine.
J Trauma Acute Care Surg. 2017 Feb;82(2):287-292. doi: 10.1097/TA.0000000000001282.
Trauma-induced coagulopathy (TIC) is commonly seen among patients with severe injury. The dynamic process of TIC is characterized by variability of the features of the disease.
A model of TIC was created. Hemodilution was produced by mixing the blood with 40% Tris/saline solution, fibrinolysis by treating the blood with 160 ng/mL tPA, acidosis by adding 1.2 mg/mL lactic acid achieving pH 7.0 to 7.1, and hypothermia by running the assay at 31°C. Intact blood tested at 37°C served as control. Clot formation was evaluated using rotation thromboelastometry. Platelet adhesion and aggregation were assayed at a shear rate of 1800 s(-) using Impact-R device.
Clotting time was not affected by any of the TIC constituents used. Clotting initiation was reduced by hemodilution and further reduced by additive hypothermia. The propagation phase of blood clotting was reduced by hemodilution, further reduced by additive hypothermia, and maximally reduced if additionally combined with fibrinolysis. No effect of fibrinolysis on clot propagation was observed at 37°C. Maximum clot firmness was reduced by hemodilution, further reduced by additive fibrinolysis, and maximally reduced if additionally combined with hypothermia. No effect of hypothermia on clot strength was observed in the absence of fibrinolysis. Platelet adhesion (percentage of surface coverage) and aggregation (aggregate size) under flow condition were reduced by hemodilution and further reduced by additive acidosis. Introduction of tPA to diluted blood had no effect on platelet function.
The study revealed a differential effect of TIC constituents-hemodilution, hypothermia, fibrinolysis, and acidosis-on clot formation and platelet function. The effect of one factor may influence that of another factor. These data may be helpful to better understand the pathogenesis of TIC and to elaborate an individually tailored treatment strategy.
A new model of TIC is created. Contribution of various constituents to pathogenesis of TIC and their interactions are evaluated.
创伤性凝血病（TIC）在重伤患者中很常见。TIC的动态过程具有疾病特征的变异性。
建立了TIC模型。通过将血液与40%的Tris/盐溶液混合产生血液稀释，用160 ng/mL组织型纤溶酶原激活剂（tPA）处理血液产生纤维蛋白溶解，添加1.2 mg/mL乳酸使pH值达到7.0至7.1产生酸中毒，并在31°C下进行测定产生低温。在37°C下测试的全血作为对照。使用旋转血栓弹力图评估凝血形成。使用Impact-R装置在1800 s(-1)的剪切速率下测定血小板黏附和聚集。
凝血时间不受所使用的任何TIC成分的影响。血液稀释会降低凝血起始，而加性低温会进一步降低。血液稀释会降低凝血的传播阶段，加性低温会进一步降低，如果再加上纤维蛋白溶解则会最大程度地降低。在37°C下未观察到纤维蛋白溶解对凝血传播的影响。最大凝块硬度会因血液稀释而降低，加性纤维蛋白溶解会进一步降低，如果再加上低温则会最大程度地降低。在没有纤维蛋白溶解的情况下，未观察到低温对凝块强度的影响。血液稀释会降低流动条件下的血小板黏附（表面覆盖百分比）和聚集（聚集体大小），加性酸中毒会进一步降低。将tPA引入稀释血液对血小板功能没有影响。
该研究揭示了TIC成分——血液稀释、低温、纤维蛋白溶解和酸中毒——对凝血形成和血小板功能的不同影响。一个因素的影响可能会影响另一个因素的影响。这些数据可能有助于更好地理解TIC的发病机制，并制定个性化的治疗策略。
建立了一种新的TIC模型。评估了各种成分对TIC发病机制的贡献及其相互作用。
