U.S. Army Institute of Surgical Research, Fort Sam, Houston TX 78234, USA.
Shock. 2013 May;39(5):440-6. doi: 10.1097/SHK.0b013e31829040e3.
Acute coagulopathy of trauma (aCOT) is a state of disordered coagulation developing soon after severe injury and blood loss and has been defined in the clinical literature as an elevation in prothrombin time (PT) and activated partial thromboplastin time (aPTT).
The purpose of this study was to develop a rat model of aCOT resulting from polytrauma and hemorrhage and showing an elevation in PT and aPTT.
Sprague-Dawley rats (300-400 g) were anesthetized with isoflurane. Polytrauma was induced by damaging 10 cm of small intestines, the right and medial liver lobes, the right leg skeletal muscle, and fracture of the right femur. Rats were hemorrhaged 40% of their estimated blood volume. No resuscitation was given. Venous and arterial blood samples were taken at times up to 4 h.
Polytrauma and hemorrhage resulted in a significant rise in PT, aPTT, potassium, lactate, and glucose. There was a significant decrease in plasma bicarbonate, base excess, and sodium. Blood urea nitrogen and creatinine rose steadily throughout the 4 h indicative of progressive renal failure. Hematocrit decreased significantly immediately after hemorrhage and trauma indicating a movement of fluid into the vascular space from extravascular sources, which was mirrored by a decrease in plasma fibrinogen concentration. In contrast, platelet count initially decreased, rose at 2 h, and decreased again at 3 to 4 h, indicating that platelets were released into the vascular space. The change in platelet count was mirrored by the changes in thrombin-antithrombin and plasmin-antiplasmin complexes. Rotational thromboelastometry showed complex changes. Clotting firmness fell initially, rose at 2 h, and fell again at 3 to 4 h similar to the changes in platelet count. α Angle was elevated, and clotting time was shortened over the 4 h. Treatment with cytochalasin D (platelet function inhibitor) eliminated the increases in clotting firmness and thrombin generation seen at 2 h with rising platelet count.
This model of aCOT in rats showed complex changes in clotting parameters over 4 h that included a rise in PT and aPTT. At 4 h, there was a decrease in clotting firmness, even though the clot formation was faster (elevated α angle and decrease in clotting time). The decrease in clotting firmness correlated with falling fibrinogen and platelet count. This model affords an opportunity to evaluate interventions in the treatment of aCOT.
创伤后急性凝血病(aCOT)是一种在严重损伤和失血后很快出现的凝血功能紊乱状态,在临床文献中被定义为凝血酶原时间(PT)和活化部分凝血活酶时间(aPTT)升高。
本研究旨在建立一种由多发伤和失血引起的大鼠 aCOT 模型,该模型表现为 PT 和 aPTT 升高。
用异氟烷麻醉 Sprague-Dawley 大鼠(300-400 g)。通过损伤 10 cm 小肠、右肝中叶和右大腿骨骼肌以及右股骨骨折来诱导多发伤。大鼠失血量为估计血容量的 40%。未给予复苏。在多达 4 小时的时间内采集静脉和动脉血样。
多发伤和失血导致 PT、aPTT、钾、乳酸和葡萄糖显著升高。血浆碳酸氢盐、碱剩余和钠显著下降。血尿素氮和肌酐在 4 小时内持续升高,表明肾功能进行性衰竭。血细胞比容在出血和创伤后立即显著下降,表明液体从血管外来源转移到血管内空间,这与血浆纤维蛋白原浓度的下降相吻合。相反,血小板计数最初下降,在 2 小时时升高,在 3 至 4 小时时再次下降,表明血小板被释放到血管空间。血小板计数的变化与凝血酶-抗凝血酶和纤溶酶-抗纤溶酶复合物的变化相吻合。旋转血栓弹性描记术显示出复杂的变化。凝血硬度最初下降,在 2 小时时升高,在 3 至 4 小时时再次下降,与血小板计数的变化相似。α 角升高,凝血时间在 4 小时内缩短。用细胞松弛素 D(血小板功能抑制剂)治疗可消除 2 小时时血小板计数升高导致的凝血硬度和凝血酶生成增加。
本研究建立的大鼠 aCOT 模型在 4 小时内凝血参数发生复杂变化,包括 PT 和 aPTT 升高。在 4 小时时,尽管凝血形成更快(α角升高,凝血时间缩短),但凝血硬度下降。凝血硬度的下降与纤维蛋白原和血小板计数的下降相关。该模型为评估治疗 aCOT 的干预措施提供了机会。