Improving evidence on anticoagulant therapies for venous thromboembolism in children: key challenges and opportunities.
Venous thromboembolism (VTE) is increasingly diagnosed in pediatric patients, and anticoagulant use in this population has become common, despite the absence of US Food and Drug Administration (FDA) approval for this indication. Guidelines for the use of anticoagulants in pediatrics are largely extrapolated from large randomized controlled trials (RCTs) in adults, smaller dose-finding and observational studies in children, and expert opinion. The recently FDA-approved direct oral anticoagulants (DOACs), such as dabigatran, rivaroxaban, apixaban, and edoxaban, provide potential advantages over oral vitamin K antagonists and subcutaneous low-molecular-weight heparins (LMWHs). However, key questions arise regarding their potential off-label clinical application in pediatric thromboembolic disease. In this Perspective, we provide background on the use of LMWHs such as enoxaparin as the mainstay of treatment of pediatric provoked VTE; identify key questions and challenges with regard to DOAC trials and future DOAC therapy in pediatric VTE; and discuss applicable lessons learned from the recent pilot/feasibility phase of a large multicenter RCT of anticoagulant duration in pediatric VTE. The challenges and lessons learned present opportunities to improve evidence for anticoagulant therapies in pediatric VTE through future clinical trials.
Department of Pediatrics and Department of Medicine, Division of Hematology, Johns Hopkins University School of Medicine, Baltimore, MD; All Children's Research Institute, All Children's Hospital Johns Hopkins Medicine, St. Petersburg, FL;
Neil A
NA
Goldenberg
Department of Pediatrics and.
Clifford M
CM
Takemoto
Department of Pediatrics, Hematology-Oncology Section, Baylor College of Medicine, Houston, TX; Texas Children's Cancer and Hematology Centers, Texas Children's Hospital, Houston, TX;
Donald L
DL
Yee
Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado-Anschutz Medical Campus, Aurora, CO;
John M
JM
Kittelson
Department of Pediatrics, Division of Cardiology, University of Alberta Faculty of Medicine, Edmonton, AB, Canada; and Stollery Children's Hospital, Edmonton, AB, Canada.
M Patricia
MP
Massicotte
D000328:Adult; D000367:Age Factors; D000925:Anticoagulants / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic / Q000379:methods; D000069604:Dabigatran / Q000494:pharmacology / Q000627:therapeutic use; D019468:Disease Management; D019317:Evidence-Based Medicine; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D015337:Multicenter Studies as Topic; D017410:Practice Guidelines as Topic; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D011728:Pyridones / Q000494:pharmacology / Q000627:therapeutic use; D000069552:Rivaroxaban / Q000494:pharmacology / Q000627:therapeutic use; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use; D054556:Venous Thromboembolism / Q000188:drug therapy* / Q000517:prevention & control
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D011720:Pyrazoles; D011725:Pyridines; D011728:Pyridones; D013844:Thiazoles; C522181:apixaban; D000069552:Rivaroxaban; D000069604:Dabigatran; C552171:edoxaban