Direct oral anticoagulants toxicity in children: an overview and practical guide

ABSTRACT

Introduction

By increasing use of direct oral anticoagulants (DOACs) in adults and children, gradual increase in the number of intentional or unintentional DOAC poisonings among children is suspected in the near future. Hence, clinicians and pharmacists need to be familiar with the clinical features and management of DOAC-toxicity among pediatric population.

Areas covered

This article provides an overview and practical guide to DOAC-toxicity in pediatrics according to the available clinical evidence.

Expert opinion

Based on limited available data, accidental pediatric ingestion of DOACs can be managed by supportive care in most cases. However, serious toxicity may occur following massive overdose, in presence of underlying disorders (renal or hepatic dysfunction) and concurrent anticoagulant therapy. Activated charcoal is recommended for known recent ingestion of DOACs (within 2–4 hours) to reduce the gastrointestinal absorption. Supportive interventions including local hemostatic measures and volume resuscitation are the cornerstone of management of bleeding. Vitamin K and fresh frozen plasma are ineffective for DOAC reversal and thus are not recommended. Currently, safety and efficacy data regarding the use of specific reversal agents (including idarucizumab and andexanet alfa) and 3-factor or 4-factor prothrombin complex concentrate (PCC) or activated PCC (aPCC) among children with DOAC-associated bleeding are lacking.

KEYWORDS:

• Apixaban
• children
• dabigatran
• direct oral anticoagulants
• poisoning
• rivaroxaban
• toxicity

Article highlights

• Based on limited available data, accidental pediatric ingestion of DOACs can be managed by supportive care in most cases.

• Serious toxicity may occur following massive overdose, in presence of underlying disorders (renal or hepatic dysfunction) and concurrent anticoagulant therapy.

• The dTT, ECA, and ECT are standard coagulation tests for dabigatran quantitation. If these tests are not available, then TT and aPTT are alternatives for qualitative assessment.

• Anti-Xa assay is the preferred coagulation test for quantitation of apixaban and rivaroxaban. When the anti-Xa assay is not available, PT is an alternative for qualitative assessment.

• Activated charcoal is recommended for known recent ingestion of DOACs (within 2-4 hours) to reduce the gastrointestinal absorption.

• Supportive interventions including local hemostatic measures and volume resuscitation are the cornerstone of management of bleeding.

• Vitamin K and fresh frozen plasma are ineffective for DOAC reversal and thus are not recommended.

• Currently, safety and efficacy data regarding the use of specific reversal agents (including idarucizumab and andexanet alfa) and 3-factor or 4-factor prothrombin complex concentrate (PCC) or activated PCC (aPCC) among children with DOAC-associated bleeding are lacking.

Authors’ contributions

All authors contributed to the study conception and design. The literature search and data analysis were performed by M Daei and Z Heidari. The first draft of the manuscript was written by M Daei, G Abbasi and Z Heidari and H Khalili revised it. All authors read and approved the final manuscript.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Data availability

The data that support the findings of this study are available from the corresponding author on reasonable request.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14740338.2022.2110236

Additional information

Funding

This paper was not funded.