Spotlight on animal models of acute traumatic coagulopathy: an update
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Critically injured persons suffer trauma, hemorrhage, and high mortality. A subset of such patients develops early coagulation dysfunction characterized as acute traumatic coagulopathy (ATC), with a poor prognosis. The mechanisms contributing to ATC remain incompletely understood. Notwithstanding some successes in conducting clinical trials in early traumatic coagulopathy, conducting clinical research in ATC is ethically and logistically challenging. In vitro studies cannot capture the complex pathophysiological interplay between blood, vasculature, and organ systems relevant to ATC. Animal models are therefore vital for understanding ATC and to test interventions. Previous systematic reviews of animal models of ATC covered progress up to 2014. The current review aimed to extend that coverage to the end of 2021. A structured systematic search of MEDLINE/PubMed was carried out and identified 56 relevant publications. Unlike in previous reviews, where pig models predominated, rat and pig models contributed equally (19 studies each), and non-human primate models entered the field. Most studies now featured defined trauma (39 of 56), and hemorrhage controlled by pressure or volume (42 studies), with some documenting that both were necessary to induce ATC. Most studies documented coagulopathy using clotting or viscoelastometric assays and created an endogenous coagulopathy not dependent on iatrogenic dilution. As before, the diversity of species and experimental protocols may limit the translatability of the identified studies. Thus, while animal research has become more aligned to clinical realities since 2014, further efforts are required to unravel ATC mechanisms and enable the prediction and evaluation of optimal clinical interventions.