Ex vivo reversal of the anticoagulant effects of edoxaban

- Reversal of edoxaban by rFVIIa or FEIBA ex vivo
- Therapeutic and supratherapeutic doses of edoxaban were used
- rFVIIa and FEIBA reversed effects on PT, aPTT, and anti-FXa
- Studies are needed to determine the clinical implications of these results

IntroductionEdoxaban is an oral, once-daily direct factor Xa (FXa) inhibitor. Although rapidly cleared, strategies to reverse edoxaban-mediated effects on anticoagulation are needed in cases of excessive bleeding or emergency. This study evaluated the effect of two prohemostatic agents, recombinant factor VIIa (rFVIIa) and factor VIII inhibitor bypass activity (FEIBA), on the anticoagulatory effects of supratherapeutic concentrations of edoxaban in human whole blood ex vivo.Materials and MethodsBlood samples were collected from six healthy volunteers. Edoxaban (500 or 1000 ng/mL), alone or followed by rFVIIa (0.8 or 1.8 μg/mL) or FEIBA (0.75 or 1.5 U/mL), was added to an aliquot of each sample. Biomarkers, including prothrombin time (PT), activated partial thromboplastin time (aPTT), extrinsic FXa activity (anti-FXa), intrinsic factor X activity, and D-dimer, were assessed at 0.25, 0.5, 1, 2, and 4 hours after adding rFVIIa or FEIBA.ResultsDecreases in measures of PT (p < 0.0001), aPTT (p < 0.0001), and anti-FXa (p < 0.0001) were observed when rFVIIa or FEIBA was added to edoxaban-containing blood samples. Intrinsic FX activity was increased up to 20% and 31% of normal in the presence of edoxaban by rFVIIa and FEIBA, respectively. The impact of these agents on the anticoagulant effects of edoxaban were observed within 15 minutes and remained relatively unchanged at each timepoint thereafter.ConclusionsThe findings of this ex vivo study suggest that rFVIIa and FEIBA rapidly reversed edoxaban-mediated anticoagulation effects based on PT and aPTT, but had minimal effect based on intrinsic FX activity. No dose response was observed for rFVIIa or FEIBA.