title: Implementation of the ISTH classification of non-overt DIC in a thromboplastin induced rabbit model.
abstract: Validation of animal models of disseminated intravascular coagulation (DIC) to human DIC is crucial in order to translate findings in research models to treatment modalities for DIC in humans. ISTH classifications of overt and non-overt human DIC have proven to have a high diagnostic accuracy, but the scoring systems have rarely been applied to animal models of DIC. In this study, we use rabbit brain thromboplastin (thromboplastin) to induce DIC in a rabbit model and test the applicability of the ISTH criteria for standardized diagnosis of DIC. Cardiovascular and haematological parameters from rabbits, either saline-injected or administered 0.625, 1.25, 2.5 or 5 mg thromboplastin/kg as a single bolus, were collected at four timepoints over a 90 minute period. All groups of rabbits were scored at each time point according to the ISTH diagnostic criteria for non-overt DIC. Injection of 5 mg thromboplastin/kg was lethal. For the remaining groups, a dose dependent decrease in blood pressure, platelet count and fibrinogen level together with a dose dependent increase in prothrombin time, activated partial thromboplastin time, level of thrombin-antithrombin complexes, fibrin degradation products and number of thrombi in lung vasculature was seen. The administration of a bolus of 1.25 - 2.5 mg thromboplastin/kg to rabbits induced a reproducible dose dependent model of non-overt DIC according to the ISTH diagnostic criteria. We conclude that the non-overt ISTH score can be applied to evaluate severity and progression of DIC in a standardized manner in this thromboplastin induced rabbit model.
authors.affiliation: Novo Nordisk A/S, Måløv, Denmark. LBth@novonordisk.com
authors.forename: Line
authors.initials: L
authors.lastname: Olrik Berthelsen
authors.forename: Annemarie
authors.initials: A
authors.lastname: Thuri Kristensen
authors.forename: Bo
authors.initials: B
authors.lastname: Wiinberg
authors.forename: Mikael
authors.initials: M
authors.lastname: Tranholm
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004211:Disseminated Intravascular Coagulation / Q000139:chemically induced / Q000145:classification* / Q000175:diagnosis; D004305:Dose-Response Relationship, Drug; D005260:Female; D005340:Fibrinogen / Q000187:drug effects; D010976:Platelet Count; D011517:Prothrombin Time; D011817:Rabbits; D013925:Thromboplastin / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D005340:Fibrinogen; D013925:Thromboplastin