Spotlight on animal models of acute traumatic coagulopathy: an update |
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| Affiliation: | 1. Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada;2. Medical Affairs and Innovation, Canadian Blood Services, Hamilton, Ontario, Canada;3. Medical Affairs and Innovation, Canadian Blood Services, Vancouver, British Columbia, Canada;4. Centre for Blood Research, University of British Columbia, Vancouver, British Columbia, Canada;1. Fundação Pró-Sangue - Hemocentro de São Paulo, São Paulo, SP, Brazil;2. Disciplina de Hematologia, Hemoterapia e Terapia Celular da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil;3. Disciplina de Ciências Médicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil;4. Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, USA;5. Institute of Tropical Medicine, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil;6. Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil;7. Instituto do Tratamento do Câncer Infantil, São Paulo, Brazil;8. Laboratório de Investigação Médica 31 (LIM-31) – Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil;1. Department of Anaesthesia and Intensive Care Medicine III, Fundeni Clinical Institute, Fundeni Street No. 258, Bucharest, 022328, Romania;2. Evangelical Hospital Vienna, 1180, Vienna, Austria;3. Sigmund Freud Private University, Medical Faculty, Campus Prater, 1020, Vienna, Austria;4. “Carol Davila” University of Medicine and Pharmacy, Dionisie Lupu Street No. 37, Bucharest, 020021, Romania;1. Department of Hematology, Instituto de Investigación Sanitaria San Carlos (IdISSC), Hospital Clínico San Carlos (HCSC), Madrid, Spain;2. Department of Emergency, Instituto de Investigación Sanitaria San Carlos (IdISSC), Hospital Clínico San Carlos (HCSC), Madrid, Spain;3. Platelet Research Lab, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain;4. Dept. of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands;5. Dept. of Molecular Hematology, Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands;6. Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany;7. Department of Medicine, University of Oviedo, Oviedo, Spain;1. Department of Environmental Health, National Institute of Public Health, 351-0197, Wako, Japan;2. Hiroshima High-Precision Radiotherapy Cancer Center, 732-0057, Hiroshima, Japan;3. Department of Radiation Oncology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 734-8551, Hiroshima, Japan;1. Servicio de Hemoterapia, Hospital Muñiz, Uspallata 2272, Buenos Aires, Argentina;2. Hospital de Pediatría SAMIC "Prof. Dr. Juan Pedro Garrahan", Pichincha 1890, Buenos Aires, Argentina;3. Colegio Nacional de Buenos Aires, Universidad de Buenos Aires, Bolivar 263, Buenos Aires, Argentina |
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| Abstract: | 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. |
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| Keywords: | Trauma Hemorrhage Coagulopathy Coagulation Animal models |
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