Persistence of platelet thrombus formation in arterioles of mice lacking both von Willebrand factor and fibrinogen

We used intravital microscopy to observe the formation of platelet plugs in ferric chloride-injured arterioles of live mice. With this model, we evalu ated thrombus growth in mice lacking von Willebrand factor (vWF) and fibrin ogen (Fg), the two key ligands known to mediate platelet adhesion and aggre gation. In vWF(-/-) mice, despite the presence of arterial shear, delayed p latelet adhesion occurred and stable thrombi formed, In many mice, a persis ting high-shear channel never occluded. Abundant thrombi formed in Fg(-/-) mice, but they detached from the subendothelium, which ultimately caused do wnstream occlusion in all cases. Surprisingly, mice deficient in both VWF a nd Fg successfully formed thrombi with properties characteristic of both mu tations, leading to vessel occlusion in the majority of vessels, platelets of these doubly deficient mice specifically accumulated fibronectin in thei r alpha-granules, suggesting that fibronectin could be the ligand supportin g the platelet aggregation.