In vitro assessment of edoxaban anticoagulant effect in pediatric plasma.

INTRODUCTION

Anticoagulant therapy in pediatric patients remains an issue and safer therapies, such as direct oral anticoagulants could overcome the limitations of conventional anticoagulant treatments in this population. Edoxaban, a factor Xa inhibitor, is used for the prevention and treatment of venous thromboembolism. Due to its pharmacokinetic characteristics, edoxaban is a promising candidate molecule for children. This study compared edoxaban in vitro effect in children and adults.

MATERIALS AND METHODS

Blood samples were prospectively collected from 87 adults and 97 children (n = 12: <2 year-old; n = 8: 2-4 year-old; n = 9: 5-7 year-old; n = 14: 8-9 year-old; n = 10: 10-13 year-old; n = 15: 14-15 year-old; and n = 29: 16-18 year-old). Plasma samples were supplemented in vitro with edoxaban to a final concentration of 50, 150 or 300 ng/mL, and then edoxaban effect on prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen (Clauss assay), specific anti-factor Xa activity and thrombin generation assay (TGA) (with 5pM tissue factor and 4 nM phospholipids) was evaluated.

RESULTS

PT, aPTT, and specific anti-Xa activity exhibited similar dose-dependent responses to edoxaban in the different age groups. The reduction of thrombin peak, the most edoxaban-sensitive TGA parameter, was similar in adults and children, but for the youngest group (<2 year-old) where the peak value reduction (median [Q1-Q3]) was higher than in adults (51% [44-59] versus 40% [32-46], p < 0.01; 74% [63-80] versus 65% [58-70], p < 0.05; and 84% [73-88] versus 76% [70-80], p < 0.05 for 50, 150 and 300 ng/mL edoxaban, respectively).

CONCLUSIONS

Edoxaban in vitro effect are comparable in children and adults except in the <2-year-old group.