Antithrombotic activity and bleeding evaluation of FXI ASO alone or in combination with clopidogrel in an aortic arterial thrombosis model. As described in “FeCl3-induced aortic thrombosis,” mice were treated with saline (“0”) or FXI ASO (dose 10 mg/kg or 20 mg/kg twice weekly for 3 weeks), either alone or in combination with clopidogrel (3 mg/kg), and thrombosis was induced 4 hours after the final dose of clopidogrel by exposing the descending aorta to a FeCl3 solution (A). Effects of FXI ASO or FXa small-molecule inhibitor in combination with clopidogrel on bleeding in mice. As described in “Anticoagulant coadministration studies,” mice were treated with increasing dose levels of clopidogrel as indicated, either alone or in combination with FXI ASO (20 mg/kg) (B) or in combination with a FXa small-molecule inhibitor (0.5 mg/kg) (C), and blood loss was determined using a mouse tail vein bleeding assay.
