Use of Direct Oral Anticoagulants in Children and Adolescents

Abstract

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.

Zusammenfassung

Während der Bedarf an Antikoagulation bei Kindern in den letzten Jahrzehnten zugenommen hat, werden die Therapierichtlinien der derzeit verwendeten Antikoagulantien, einschließlich niedermolekularem Heparin (LMWH) und Vitamin K-Antagonisten (VKA), immer noch aus den Empfehlungen für Erwachsene extrapoliert, da nie gut konzipierte klinische Studien an Kindern durchgeführt wurden. Dieser Ansatz ist aufgrund spezifischer pädiatrischer Merkmale des hämostatischen Systems und der Pathophysiologie der Thrombose nicht optimal. Diese Antikoagulantien weisen auch mehrere Nachteile auf, die eine optimale Antikoagulation von pädiatrischen Patienten, insbesondere von Neugeborenen und Säuglingen, weiter behindern. Die neuen direkten oralen Antikoagulantien (DOACs), die das Potenzial haben, diese Nachteile zu überwinden, wurden bei Erwachsenen umfassend untersucht und stellen eine valide Alternative zu LMWH und VKA für die Antikoagulation in der Erwachsenenpopulation dar. Derzeit laufen mehrere pädiatrische Studien mit allen zugelassenen DOACs, die spezifische pädiatrische Formulierungen sowie alters- und gewichtsangepasste Dosisrichtlinien enthalten. Erste Ergebnisse der Phase-III-Studien zeigen, dass DOACs zur Behandlung und Prävention thrombotischer Ereignisse bei Kindern mit unterschiedlichen Grundkrankheiten mindestens so effizient und sicher sind wie LMWH und VKA. Dieser Übersichtsartikel fasst die verfügbaren Daten aus abgeschlossenen und laufenden kontrollierten Studien zu DOACs bei Kindern und Jugendlichen zusammen.

Keywords

direct oral anticoagulants - anticoagulation - children - thrombosis

Schlüsselwörter

direkte orale Antikoagulantien - Antikoagulation - Kinder - Thrombose

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