Critical Review of Large Animal Models for Central Deep Venous Thrombosis

Objective: To review the existing literature on large animal models of central venous thrombosis (CVT) and to evaluate its relevance in regard to the development and testing of dedicated therapeutics applicable to humans. Methods: A systematic literature search was conducted in PubMed and Embase. Articles describing an in vivo experimental protocol of CVT in large animals, involving the iliac vein and/or the vena cava and/or the brachiocephalic vein, were included. The primary aim of the study, animal characteristics, experimental protocol, and thrombus evaluation were recorded. Results: Thirty-eight papers describing more than 30 different protocols were included. Animals used were pigs (53%), dogs (21%), monkeys (24%), and cattle (3%). The median number of animals per study was 12. Animal sex, strain, and weight were missing in 18 studies (47%), seven studies (18%), and eight studies (21%), respectively. CVT was always induced by venous stasis: solely (55%), or in addition to hypercoagulability (37%) or endothelial damage (10%). The size of the vessel used for thrombus creation was measured in four studies (10%). Unexpected animal death occurred in nine studies (24%), ranging from 3% to 37% of the animals. Twenty-two studies (58%) in the acute phase and 31 studies in the chronic phase (82%) evaluated the presence or absence of the thrombus created, and its occlusive characteristic was reported, respectively, in five and 17 studies. Histological examination was performed in 24 studies (63%) with comparison to human thrombus in one study. Conclusion: This review showed advantages and weaknesses of the existing large animal models of CVT. Future models should insist on more rigour and consistency in reporting animal characteristics, as well as evaluating and comparing the thrombus created to human thrombus.