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 2.5mg thromboplastin/kg bolus and a 15minutes 1.25mg thromboplastin/kg infusion, were determined at four time points over a 90minute 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.

Abbreviations: ISTH, International Society on Thrombosis and Haemostasis, DIC, disseminated intravascular coagulation, FDP, fibrin degradation product, PT, prothrombin time, AT, antithrombin, TAT, thrombin-antithrombin, PC, protein C, TEG, thromboelastography, FVIIa, activated factor VII, LAL, Limulus Amebocyte Lysate, BP, blood pressure, HR, heart rate, RVPmax, maximal right ventricular pressure, ECG, electrocardiogram, cTnI, cardiac troponin I, aPTT, activated partial thromboplastin time, ELISA, enzyme-linked immunoadsorbent assay, MA, maximal amplitude, R, clotting time, HE, hematoxylin-eosin, PTAH, phosphotungstic acid hematoxylin, WBC, white blood cell

Keywords: Disseminated intravascular coagulation (DIC), Animal model, Rabbit, Thromboplastin, Overt DIC