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Semin Thromb Hemost 2021; 47(06): 643-653
DOI: 10.1055/s-0041-1725944
Review Article

Efficacy and Safety of Non-Vitamin K Antagonist Oral Anticoagulants in Pediatric Venous Thromboembolism Treatment and Thromboprophylaxis: A Systematic Review of the Literature

Authors

  • Joshua W. Branstetter   *

    1   Department of Pharmacy, Children's Healthcare of Atlanta, Atlanta, Georgia

  • Amy L. Kiskaddon   *

    2   Department of Pharmacy, The Johns Hopkins All Children's Hospital, St. Petersburg, Florida
    3   Johns Hopkins All Children's Institute for Clinical and Translational Research, St. Petersburg, Florida

  • Madeleine A. King

    4   Department of Pharmacy, C.S. Mott Children's Hospital, Ann Arbor, Michigan

  • Carli Coalter

    5   College of Pharmacy, Union University, Jackson, Tennessee

  • Kimberly M. Grubbs

    6   Department of Pharmacy, Medical University of South Carolina, Charleston, South Carolina

  • Hunter Fly

    7   Department of Pharmacy, Le Bonheur Children's Hospital, Memphis, Tennessee

  • Christoph Male

    8   Department of Paediatrics, Medical University of Vienna, Austria

  • Leonardo Brandão

    9   Division of Haematology/Oncology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
    10   Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada

  • Neil A. Goldenberg

    3   Johns Hopkins All Children's Institute for Clinical and Translational Research, St. Petersburg, Florida
    11   Thrombosis Program, Johns Hopkins All Children's Hospital, St. Petersburg, Florida
    12   Department of Pediatrics and Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
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Abstract

Venous thromboembolism (VTE) in children can lead to significant morbidity and mortality. Traditionally, treatment for thrombotic events in pediatric patients has been limited mainly to unfractionated heparin, low-molecular-weight heparin (LMWH), or vitamin K antagonists. Since the first non–vitamin K antagonist oral anticoagulant (NOAC) was approved for adult use, these agents have gained popularity for a variety of indications. This is largely due to their ease of administration, favorable pharmacokinetic and pharmacodynamic profile, decreased food interactions, and decreased need for therapeutic drug monitoring. Treating and preventing VTE with traditional anticoagulants in pediatric patients presents many challenges. This systematic review evaluated the current literature regarding pediatric NOAC trials. Additionally, based on an up-to-date query of clinicaltrials.gov, we detail current ongoing and as-yet unpublished clinical trials, study outcomes, and projected completion dates. Published pediatric NOAC trials have included 1,007 total children to date and have ranged from phase 1 to 4, with “indications” including both thromboembolism prophylaxis and VTE treatment. Three recent phase 3 trials, specifically involving rivaroxaban and dabigatran, have shown the agents to be at least as effective as traditional anticoagulants for acute and/or extended VTE treatment, with low frequency of recurrent thrombosis and clinically significant bleeding rates. Additionally, specially developed and tested pediatric formulations have allowed for accurate and reliable dosing, oral administration, stable pharmacokinetics and pharmacodynamics, and fewer drug or food interactions. Ongoing trials, anticipated for completion in the next few years, will reveal important information with regard to thromboembolism prophylaxis in special pediatric subpopulations and settings.

Keywords

pediatric VTE - thromboprophylaxis - NOACs

* These authors contributed equally, as co-first authors.




Publication History

Article published online:
10 May 2021

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