Increased Vascular Wall Thrombogenicity Combined With Reduced Blood Flow Promotes Occlusive Thrombus Formation in Rabbit Femoral Artery

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Abstract
Objective— Plaque disruption does not always result in complete thrombotic occlusion. The mechanism of arterial thrombus propagation remains unclear. Methods and Results— We studied how vascular wall thrombogenicity and blood flow reduction affect thrombus propagation using a rabbit model of single and repeated balloon injury. After balloon injury of the normal femoral artery, the blood flow was reduced to 50%, 25%, or 10% (n=5). Small mural thrombi composed of aggregated platelets were produced, but no occlusive thrombi developed in any flow reduction. Three weeks after the first balloon injury, neointima with tissue factor expression and increased procoagulant activity was developed. Balloon injury of the neointima with the same blood flow reduction (n=5) induced fibrin-rich thrombus formation. Additionally, injury with flow reduced to 25% and 10% promoted thrombus propagation resulting in vessel occlusion within 160±18 and 71±17 seconds, respectively. An injection of anti-von Willebrand factor (vWF) mo... We demonstrated in an animal model that increased vascular wall thrombogenicity combined with a blood flow reduction (>75%) promoted occlusive thrombus formation that was prevented by inhibiting plasma vWF. Reduced blood flow at plaque disruption sites might contribute to thrombus propagation and lead to acute coronary syndromes.