Murine models in the evaluation of heparan sulfate-based anticoagulants.

Abstract

Evaluating anticoagulants in animal thrombosis models is a standard component of preclinical drug testing. Mice are frequently used for these initial evaluations because a variety of thrombosis models have been developed and are well characterized in this species, and the animals are relatively inexpensive to maintain. Because mice have a natural resistance to forming intravascular thrombi, vessel injury is required to induce intravascular clot formation. Several methods have been established for inducing arterial or venous thrombosis in mice. For the purpose of testing heparin-based drugs, we adapted a well-established model in which thrombus formation in the carotid artery is induced by exposing the vessel to ferric chloride. For studying anticoagulant effects on venous thrombosis, we use a model in which the inferior vena cava is ligated and the size of the resulting clots is measured. The most common adverse effect of anticoagulation therapy is bleeding. The effect of heparin-based anticoagulants can be tested in mice in a simple tail bleeding assay.