title: Animal models of DIC and their relevance to human DIC: a systematic review.
abstract: Disseminated intravascular coagulation (DIC) is a severe clinical condition with activation of coagulation and fibrinolysis. Its diagnosis is based on the International Society of Thrombosis and Haemostasis (ISTH) scoring system of DIC. Animal models of DIC, used to investigate pathophysiology and evaluate treatments, have not been developed in a standardized way, which impedes comparison between models and translation to the human setting. In the current review of animal models of DIC an overview of species, inducers, and dosing regimens is provided. Diagnostic approaches are compared in the light of the ISTH score and treatments tested in animal models of DIC are summarized. Systematic analysis revealed that the rat is by far the preferred species amongst animal models of DIC and lipopolysaccharides (LPS) the preferred inducer of DIC. An overview of the reporting of ISTH DIC score parameters elucidated that only about 25% of the studies measure all of the four parameters necessary for the implementation the ISTH scoring system. Furthermore, most therapeutic interventions tested in animal models of DIC are administered prophylactically, which may be irrelevant to the clinical setting and could explain why compounds effective in preclinical animal models often fail in clinical trials. It is concluded that Implementation of a scoring system in animal models of DIC may increase the ability to compare DIC amongst animal models and improve the translational aspect of treatment effect.
authors.affiliation: Novo Nordisk A/S, Måløv, Denmark. lineberthelsen@yahoo.dk
authors.forename: Line Olrik
authors.initials: LO
authors.lastname: Berthelsen
authors.forename: Annemarie T
authors.initials: AT
authors.lastname: Kristensen
authors.forename: Mikael
authors.initials: M
authors.lastname: Tranholm
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004211:Disseminated Intravascular Coagulation; D006801:Humans; D051381:Rats; D017208:Rats, Wistar