Division of Hematology and Children's Research Center, University Children's Hospital, Zurich, Switzerland.
Hamostaseologie. 2020 Feb;40(1):64-73. doi: 10.1055/s-0039-3400491. Epub 2020 Feb 12.
While the need for anticoagulation in children has increased over the last decades, dose regimens of currently used anticoagulants, including low-molecular-weight heparin (LMWH) and vitamin K antagonist (VKA), are still extrapolated from adult guidelines because well-designed clinical trials were never performed in children. This approach is not optimal due to specific pediatric features of the hemostatic system and pathophysiology of thrombosis. These anticoagulants also present several disadvantages that further hamper optimal anticoagulation of pediatric patients, especially newborns and infants. The new direct oral anticoagulants (DOACs), which have the potential to overcome these disadvantages, were extensively investigated in adults and have become a valid alternative to LMWH and VKA for anticoagulation in the adult population. Several pediatric trials on all approved DOACs are currently ongoing, providing specific pediatric formulations and age- and weight-adjusted dose guidelines. First results of phase III trials indicate that DOACs are at least as efficient and safe as LMWH and VKA for the treatment and prevention of thrombotic events in children with different clinical conditions. This review article summarizes available data from terminated and ongoing controlled trials on DOACs in children and adolescents.
尽管过去几十年来儿童抗凝的需求有所增加，但目前使用的抗凝剂（包括低分子肝素 [LMWH] 和维生素 K 拮抗剂 [VKA]）的剂量方案仍从成人指南中推断得出，因为从未在儿童中进行过精心设计的临床试验。由于止血系统和血栓形成的病理生理学存在特定的儿科特征，这种方法并不理想。这些抗凝剂还存在一些缺点，进一步阻碍了儿科患者的最佳抗凝治疗，尤其是新生儿和婴儿。新型直接口服抗凝剂（DOACs）有可能克服这些缺点，它们在成人中得到了广泛研究，并成为成人抗凝治疗中 LMWH 和 VKA 的有效替代品。目前正在进行所有已批准的 DOAC 的多项儿科试验，提供了特定的儿科配方和按年龄和体重调整的剂量指南。III 期试验的初步结果表明，DOAC 至少与 LMWH 和 VKA 一样有效和安全，可用于治疗和预防不同临床情况下儿童的血栓事件。本文综述了已终止和正在进行的关于儿童和青少年 DOAC 的对照试验的现有数据。
