Acute Coagulopathy of Trauma in the Rat

Abstract

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.

The pathogenesis of traumatic coagulopathy

“…Endothelial cell activation, stimulated by thrombin and various cytokines, as well as hypoxia and hypoperfusion [48], generates a prothrombotic environment. Hypoperfusion plays a critical role in the pathogenesis of ATC as demonstrated in numerous clinical studies [3,6,[42][43][44][45][46][47][48][49][50][51], animal models [6,50] and in vitro experiments [22,51]. These data indicate that as shock severity increases, the PT and INR rise [4,5,7,52] and coagulation factor levels fall [6,48].…”

“…Thrombolastographic hyperfibrinolysis should perhaps be used to describe increased lysis only in relation to TEG visco-elastic measurements. There is no commonly accepted visco-elastic definition of ATC, although the candidates include: increases in clotting time and clot formation time; and loss of clot amplitude (CA) and maximal clot amplitude [40,50,75]. One group used ROTEM to define an EXTEM CA5 (CA at 5 min) value of < 36 mm as diagnostic of ATC [5].…”

Validation of acute traumatic coagulopathy in an ovine model of trauma and haemorrhage

“…porcine models with varying effects on coagulation function observed (29, 40,51,65,67,177,[200][201][202][203]. All rodent models demonstrated a minimum 20% prolongation in PT, aPTT or PT ratio (PTr) (29, 40, 65) which was attenuated by monoclonal antibodies to aPC in one study (40).…”

“…A combination of tissue injury and tissue hypoperfusion has been shown to be a necessary pre-requisite for the development of ATC in clinical studies (25,29,37,39,(87)(88)(89)(90), in vitro experiments (91) and animal models (29,40,65). A normal base deficit is not associated with coagulopathy in trauma regardless of the injury severity (29, 37, 92, 93).…”

“…Rodents have consistently demonstrated the ability to achieve clinical definitions of ATC in response to trauma and haemorrhage (29, 40,65), however they are limited by animal size and recognized differences in coagulation function (58). Pigs are the only large animal species that has been used for evaluating ATC, which would appear appropriate given the established physiological similarities between pigs and humans (66).…”