Key Points

the presence of VWF to modulate arterial thrombosis. Platelet thrombospondin 1 contributes to arterial thrombosis. Thrombospondin1 (TSP1)hasbeensuggestedasacounter receptor toplateletglycoprotein Iba that supports initial platelet adhesion in absence of von Willebrand factor (VWF). Conversely, several other studies have shown that TSP1 interacts with VWF and may play a mechanistic role in modulating thrombosis. However, the in vivo evidence to support this mechanism remains unclear. Using intravital microscopy, in a 10 % FeCl3-induced thrombosis model, we report similar platelet adhesion in Tsp1-/-/Vwf2/2 mice compared with littermate Vwf2/2 mice, suggesting that TSP1 does not mediate initial platelet adhesion in the absence of VWF. Tsp12/2mice exhibited prolonged occlusion time and a significant decrease in the rate of thrombus growth (P <.05 vs wild-type), but not in the initial platelet adhesion. Complete deficiency of VWF abrogated the rate of thrombus growth in Tsp12/2mice; therefore, we generated Tsp1-/-/Vwf1/2mice to determine whether TSP1 modulates thrombus growth under conditions of partial VWF deficiency. Tsp1-/-/Vwf1/2 mice exhibited delayed thrombus growth kinetics and prolonged occlusion time (P <.05 vs Vwf1/2). Finally, we demonstrate that platelet-derivedTSP1modulates arterial thrombosis in vivo.Weconclude that TSP1 released fromplatelets plays a mechanistic role in modulating thrombosis in the presence of VWF. (Blood. 2015;125(2):399-406