Venous thrombosis is a potentially devastating condition with a number of different causes.  It is a potential negative side-effect of hormone replacement therapies, it is a significant possible negative side effect of both cancer and anti-cancer therapies, and can be induced by airline travel, particularly in those who have a genetic predisposition to clotting problems.

Biomodels had developed and validated a reproducible and quantifiable animal model to compare the pro-thrombogenic and anti-thrombogenic activities of novel therapeutics to provide a pre-clinical means of assessing the potential benefits of new drugs and drug combinations in the reduction of the risk of promoting venous thrombosis.

In this model, C57Bl/6 mice are anesthetized and the femoral vein is surgically exposed.  A thrombus is induced by the direct application of a solution of ferric chloride (FeCl3) to the adventitial surface of the vein.  Thrombus formation is measured using intravital video microscopy alone or in conjunction with a laser Doppler flow probe to monitor vessel occlusion. In addition to the primary endpoint of time to complete occlusion, other flow parameters including a visual evaluation of blood flow using the Thrombolysis in Myocardial Infarction (TIMI) scoring scale are assessed.  This model can be used to evaluate the impact of anti-coagulants, and has been used to evaluate the potential for compounds to increase the propensity for clot formation.

Thrombosis Evaluation

To evaluate the extent of change in blood flow and the total time until cessation of blood flow following the FeCl3 application, the video from each mouse was analyzed in a blinded fashion.  The video is viewed and a Thrombolysis In Myocardial Infarction (TIMI) score of 0 (no flow), to a score of 3 (normal flow) is assigned to the observed blood flow prior to FeCl3 application and again at 30 seconds, 1, 2, 5, 10, 15, and 20 minutes after thrombus induction.  See Table below for a complete explanation of the TIMI grades.  Additionally, the time that it takes for complete vessel occlusion is also determined using video analysis.   Animals are also examined using laser Doppler to quantitatively determine alterations in blood perfusion following the thrombus induction. 

TIMI Grade

Images of thrombus induction

Representative images were captured from a video of thrombus induction in an untreated control animal.









Preclinical Venous Thrombosis Research Models | Drug Development Venous Thrombosis Models