Rational Design of an Ex Vivo Model of Thrombosis

The underlying pathogenesis of cardiovascular disease is the formation of occlusive thrombi. While many well-defined animal models recapitulate the process of intravascular thrombosis, there is a need for validated ex vivo models of occlusive thrombus formation. Using the force of gravity to provide a constant pressure gradient, we designed and validated an ex vivo model of thrombosis. Times to occlusion on a collagen matrix in our model were within the range of occlusion times observed in murine thrombosis models. Prolongation of time to occlusion in the presence of platelet alpha(IIb)beta(3) antagonists or inhibitors to thrombin or activated factor X is in agreement with established mechanisms of thrombus formation. The use of this model may be expanded to characterize the mechanisms of thrombosis and to determine the efficacy of pharmacological agents designed to prevent occlusive thrombus formation.