Format

Send to

Choose Destination
Thromb Res. 2014 Oct;134(4):909-13. doi: 10.1016/j.thromres.2014.07.036. Epub 2014 Aug 7.

Ex vivo reversal of the anticoagulant effects of edoxaban.

Author information

1
Daiichi Sankyo Pharma Development, 399 Thornall Street, Edison, NJ 08837, Edison, NJ, USA. Electronic address: Abdel.Halim@drugscan.com.
2
Cochin-Broca-Hôtel-Dieu University Hospital, 27, rue du Fg Saint-Jacques, 75679 Paris Cedex 14, France; Biomnis Laboratory, 78 avenue de Verdun, BP 110 94208 Ivry-sur-Seine Cedex, France. Electronic address: meyermichel.samama@biomnis.com.
3
Daiichi Sankyo Pharma Development, 399 Thornall Street, Edison, NJ 08837, Edison, NJ, USA. Electronic address: jmendell@dsi.com.

Abstract

INTRODUCTION:

Edoxaban 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 METHODS:

Blood samples were collected from six healthy volunteers. Edoxaban (500 or 1000 ng/mL), alone or followed by rFVIIa (0.8 or 1.8μg/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.

RESULTS:

Decreases 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.

CONCLUSIONS:

The 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.

KEYWORDS:

Anticoagulant reversal; Edoxaban; FEIBA; Factor Xa; rFVIIa

PMID:
25179520
DOI:
10.1016/j.thromres.2014.07.036
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center