Ex vivo reversal of the anticoagulant effects of edoxaban

被引:40
作者
Halim, Abdel-Baset [1 ]
Samama, Meyer M. [2 ,3 ]
Mendell, Jeanne [1 ]
机构
[1] Daiichi Sankyo Pharma Dev, Edison, NJ 08837 USA
[2] Cochin Broca Hotel Dieu Univ Hosp, F-75679 Paris 14, France
[3] Biomnis Lab, F-94208 Ivry, France
关键词
Anticoagulant reversal; Edoxaban; Factor Xa; FEIBA; rFVIIa; FACTOR XA INHIBITOR; PROTHROMBIN COMPLEX CONCENTRATE; DIRECT ORAL ANTICOAGULANTS; ACTIVATED FACTOR-VII; LONG-TERM TREATMENT; PERIOPERATIVE HEMOSTASIS; BLEEDING COMPLICATIONS; ATRIAL-FIBRILLATION; WORKING GROUP; RABBIT MODEL;
D O I
10.1016/j.thromres.2014.07.036
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 1.8 mu g/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. (C) 2014 The Authors. Published by Elsevier Ltd.
引用
收藏
页码:909 / 913
页数:5
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