CHU Clermont-Ferrand, Service d'Hématologie Biologique, Clermont-Ferrand, France; Université Clermont Auvergne, INRA, UNH, Unité de Nutrition Humaine, CRNH Auvergne, Clermont-Ferrand, France.
CHU Clermont-Ferrand, Service d'Hématologie Biologique, Clermont-Ferrand, France.
Thromb Res. 2019 Jun;178:112-118. doi: 10.1016/j.thromres.2019.04.014. Epub 2019 Apr 13.
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.
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.
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).
Edoxaban in vitro effect are comparable in children and adults except in the <2-year-old group.
儿童患者的抗凝治疗仍然是一个问题，更安全的治疗方法，如直接口服抗凝剂，可以克服这种人群中传统抗凝治疗的局限性。依度沙班是一种 Xa 因子抑制剂，用于预防和治疗静脉血栓栓塞症。由于其药代动力学特性，依度沙班是儿童的一种有前途的候选分子。本研究比较了依度沙班在儿童和成人中的体外作用。
前瞻性地从 87 名成年人和 97 名儿童（n=12：<2 岁；n=8：2-4 岁；n=9：5-7 岁；n=14：8-9 岁；n=10：10-13 岁；n=15：14-15 岁；n=29：16-18 岁）中采集血样。将血浆样本在体外加入依度沙班至终浓度为 50、150 或 300ng/ml，然后评估依度沙班对凝血酶原时间（PT）、活化部分凝血活酶时间（aPTT）、纤维蛋白原（Clauss 测定法）、抗 Xa 因子活性和血栓生成试验（TGA）（用 5pM 组织因子和 4nM 磷脂）的影响。
不同年龄组的 PT、aPTT 和抗 Xa 活性对依度沙班的剂量依赖性反应相似。凝血酶峰的降低，即最敏感的 TGA 参数，在成年人和儿童中相似，但对于年龄最小的组（<2 岁），峰降低值（中位数[Q1-Q3]）高于成年人（51%[44-59]比 40%[32-46]，p<0.01；74%[63-80]比 65%[58-70]，p<0.05；84%[73-88]比 76%[70-80]，p<0.05 用于 50、150 和 300ng/ml 的依度沙班）。
除<2 岁组外，依度沙班在儿童和成人中的体外作用相当。
