title: Purified thromboplastin causes haemostatic abnormalities but not overt DIC in an experimental 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, and we have previously established a rabbit model of non-overt DIC based on the ISTH classification of non-overt DIC. In this rabbit model, we used purified rabbit brain thromboplastin to induce DIC and test applicability of ISTH classifications of overt human DIC. Cardiovascular and haematological parameters from rabbits, either saline-injected or administered a 2.5 mg thromboplastin/kg bolus and a 15 minutes 1.25 mg thromboplastin/kg infusion, were determined at four time points over a 90 minute period. All groups of rabbits were scored at each time point according to the ISTH classifications of overt DIC. Despite the fact that injection of purified thromboplastin resulted in decreased platelet count, increased prothrombin time, activated partial thromboplastin time, level of thrombin-antithrombin complexes and fibrin degradation products, and pulmonary micro-thrombosis, none of the rabbits were diagnosed as having overt DIC according to ISTH classification. We conclude that purified thromboplastin causes haemostatic abnormalities in the rabbit but this experimental model was not diagnosed as overt DIC.
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 / Q000139:chemically induced* / Q000473:pathology; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006487:Hemostasis; D006801:Humans; D010314:Partial Thromboplastin Time; D010976:Platelet Count; D011517:Prothrombin Time; D011817:Rabbits; D013916:Thrombelastography; D013925:Thromboplastin
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D005340:Fibrinogen; D013925:Thromboplastin