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. 2024 Feb 1;143(5):389-403.
doi: 10.1182/blood.2022018966.

How I treat pediatric venous thromboembolism in the DOAC era

Rukhmi V Bhat  1 , Guy Young  2 , Anjali A Sharathkumar  3
Affiliations

How I treat pediatric venous thromboembolism in the DOAC era

Rukhmi V Bhat et al. Blood. .

Abstract

The direct oral anticoagulants (DOACs) rivaroxaban and dabigatran are newly licensed for the treatment and prevention of venous thromboembolism (VTE) in children and mark a renaissance in pediatric anticoagulation management. They provide a convenient option over standard-of-care anticoagulants (heparins, fondaparinux, and vitamin K antagonists) because of their oral route of administration, child-friendly formulations, and significant reduction in monitoring. However, limitations related to therapeutic monitoring when needed and the lack of approved reversal agents for DOACs in children raise some safety concerns. There is accumulating experience of safety and efficacy of DOACs in adults for a broad scope of indications; however, the cumulative experience of using DOACs in pediatrics, specifically for those with coexisting chronic illnesses, is sparse. Consequently, clinicians must often rely on their experience for treating VTE and extrapolate from data in adults while using DOACs in children. In this article, the authors share their experience of managing 4 scenarios that hematologists are likely to encounter in their day-to-day practice. Topics addressed include (1) appropriateness of indication; (2) use for special populations of children; (3) considerations for laboratory monitoring; (4) transition between anticoagulants; (5) major drug interactions; (6) perioperative management; and (7) anticoagulation reversal.

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Conflict of interest statement

Conflict-of-interest disclosure: R.V.B. reports being an institutional principal investigator for pediatric VTE trials funded by Pfizer and Bayer and receiving an investigator-initiated grant from the Bristol Myers Squibb–Pfizer alliance to study risk factors of neonatal thrombosis. G.Y. was an institutional principal investigator for pediatric VTE trials funded by Bayer and Daiichi-Sankyo; has received consulting fees and honoraria from Bayer and Daiichi-Sankyo; and received a licensing fee from Viatris. A.A.S. was an institutional principal investigator for pediatric VTE trials funded by the National Institutes of Health, Pfizer, and Boehringer-Ingelheim.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Schematic diagram showing the mechanism of action of DOACs. F, factor.
Figure 2.
Figure 2.
Algorithm for pediatric VTE anticoagulation management. ∗indicates severe liver or renal dysfunction, short gut syndrome, severe thrombocytopenia, ICH, or postoperative or severe trauma. VTE, venous thromboembolism; SOC, standard of care; DOAC, direct oral anticoagulant; NG, nasogastric; PO, by mouth.
Figure 3.
Figure 3.
Periprocedural management of DOACs. ∗Assuming normal renal function and platelet count >50 000 × 109/L; ^surgical bleeding risk stratification has not been studied in children.
Figure 4.
Figure 4.
Published dabigatran (DIVERSITY-phase 2b/3) dosing strategy according to formulation (VTE treatment). Dosing regimen using dabigatran capsules (A), dosing regimen using pellets (B), and dosing regimen using oral liquid formulation (OLF) (C). Adapted from Halton et al with permission from Elsevier.
See this image and copyright information in PMC

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