Acute coagulopathy of trauma in the rat.

INTRODUCTION: 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).
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.