TY - JOUR
T1 - Improving evidence on anticoagulant therapies for venous thromboembolism in children
T2 - Key challenges and opportunities
AU - Goldenberg, Neil A.
AU - Takemoto, Clifford M.
AU - Yee, Donald L.
AU - Kittelson, John M.
AU - Massicotte, M. Patricia
N1 - Publisher Copyright:
© 2015 by The American Society of Hematology.
PY - 2015/12/10
Y1 - 2015/12/10
N2 - Venous thromboembolism (VTE) is increasingly diagnosed in pediatric patients, andanticoagulantusein thispopulationhas 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 inpediatric thromboembolic disease. In this Perspective, we provide background on the use of LMWHssuch 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.
AB - Venous thromboembolism (VTE) is increasingly diagnosed in pediatric patients, andanticoagulantusein thispopulationhas 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 inpediatric thromboembolic disease. In this Perspective, we provide background on the use of LMWHssuch 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.
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U2 - 10.1182/blood-2015-06-651539
DO - 10.1182/blood-2015-06-651539
M3 - Review article
C2 - 26500341
AN - SCOPUS:84951334874
SN - 0006-4971
VL - 126
SP - 2541
EP - 2547
JO - Blood
JF - Blood
IS - 24
ER -