Objective—Fibronectin (FN) plays an important role in the formation of stable arterial thrombi at the site of vascular injury. FN containing Extra Domain A (EDA⁺FN) is absent from normal plasma, but elevated plasma levels of EDA⁺FN are found in several pathological conditions. We hypothesized that EDA⁺FN plays a special role in thrombosis.

Methods and Results—We used mouse strains constitutively including (EDA^+/+) or excluding (EDA^-/-) the EDA domain in all tissues and plasma. Using a flow chamber and the ferric-chloride injury model we found that EDA⁺FN accelerates thrombosis both in vitro and in vivo at arterial shear rates. In EDA^+/+ mice thrombi (>30 µm) grew faster when compared with EDA^WT/WT (6.6±0.2 minutes versus 8.3±0.6 minutes, P<0.05) and the mean vessel occlusion time was shorter (9.9±0.4 minutes versus 14.6±1.7 minutes, P<0.05). However, the presence of EDA⁺FN affected neither single platelet adhesion to subendothelium nor thrombosis in veins. In addition, the mortality rate of EDA^+/+ mice after collagen/epinephrine infusion was twice that of EDA^WT/WT or EDA^-/- mice.

Conclusions—Our findings reveal that EDA⁺FN has prothrombotic activity, and its presence in plasma may worsen pathological conditions in which this form is elevated.