Purpose: The new oral anticoagulants have demonstrated efficacy and safety in preventing stroke in patients with AF; however, they all lack a specific antidote in cases of emergency. A fully humanized monoclonal antibody fragment (Fab) against dabigatran is currently in development. Reversal of dabigatran etexilate (DE)-induced blood loss in a rat tail bleeding model by this Fab has been shown. While its effect against other anticoagulants is not expected, this has not been demonstrated. This study investigated whether the Fab alters the ex vivo clotting activites of warfarin, rivaroxaban and apixaban. Methods: DE (30 mg/kg), rivaroxaban (30 mg/kg), or apixaban (30 mg/kg) was administered p.o. to rats 3 times in 8 hr intervals to achieve supratherapeutic activity levels. Warfarin was administered p.o. over 3 days (0.5 mg/kg). Fab (0.69μm/kg) was administered via i.v. injection and blood plasma samples taken up to 120 minutes to test for alterations in ex vivo clotting activity. Ex vivo clotting in DE-treated rats was determined by thrombin time (TT), ecarin clotting time (ECT) and aPTT. Rivaroxaban and apixaban activity was determined by the FXa clotting assay, aPTT and PT, and warfarin activity assessed by PT. The vitamin K-dependent coagulation factor levels, FII, FVII, and FX were also tested in the presence of each anticoagulant. Results: Treating rats with DE, rivaroxaban, apixaban, or warfarin to achieve supratherapeutic levels led to a prolongation of ex vivo clotting. DE increased ECT from 10s to 90s, TT from 20s to 190s, and aPTT from 20s to 45s, whereas rivaroxaban and apixaban had no effect on aPTT or PT, but elevated the FXa clotting assay from 31s to 135s and 196s, respectively. Warfarin treatment increased PT from 12s to 100s. Injection of Fab led to a rapid reversal of all dabigatran-prolonged clotting assays within 5 minutes of injection. Similar doses of Fab had no effect on the ex vivo clotting profiles in rivaroxaban, apixaban, or warfarin treated rats. When measuring vitamin K-dependent factors, warfarin reduced factor FII and VII almost completely, factor Xa by 60%. Dabigatran temporarily reduced FII levels, this correlated with plasma levels of the drug.There was no depression on any of these factors by apixaban or rivaroxaban. Conclusions: These preliminary data show the specificity and selectivity of the Fab for dabigatran in ex vivo clotting assays, with no interaction or influence on ex vivo clotting in the presence of the oral anticoagulants warfarin, rivaroxaban, and apixaban. Thus, the dabigatran antidote is specific for reversing dabigatran-induced anticoagulation.