Anticoagulation in Pediatrics: DOACs on the Horizon

Jasmine Manning, PharmD Candidate 2019; Diane Nykamp, PharmD

Disclosures

US Pharmacist. 2019;44(5):HS8-HS12. 

In This Article

Abstract and Introduction

Abstract

Pediatric anticoagulation includes the standard therapy of warfarin, unfractionated heparin, and low molecular weight heparin. Anticoagulants are used in pediatrics, but there are limited data surrounding safety and efficacy. Although venous thrombosis is more common in adults, it also occurs in children and is usually due to the use of a central venous catheter during hospitalization. An increased incidence of venous thrombosis in pediatric patients warrants the need for more favorable therapies. Several pediatric trials are currently focusing on the use of direct oral anticoagulation therapy, with a likely shift to its use in the future.

Introduction

Traditionally, anticoagulants in the pediatric population have been indicated for the management of congenital heart defects, Kawasaki disease, and deficiencies of natural anticoagulants. Data have shown a steady increase in the use of anticoagulants for treatment of venous thrombosis (VTE) in pediatric patients, most commonly due to hospitalization (HA-VTE).[1] The most common cause of HA-VTE is an indwelling central venous catheter.1 Catheter occlusions are due in part to venous stasis, hypercoagulability, and trauma to the vessel wall. The size of the catheter presents an additional problem since children have small vessel size and may require a large-diameter catheter. Data show that HA-VTE has increased from 5.3 events per 10,000 pediatric hospital admissions in the early 1990s to a current estimate of 30 to 58 events per 10,000 pediatric hospital admissions as of 2016.[1]

The rationale and approach to anticoagulation therapy in pediatrics is much like that in the adult population, but there are unique factors to consider with pediatrics. One area of concern is initiation of therapy in pediatric patients aged less than 1 year who have not fully developed the coagulation proteins needed for certain anticoagulants to take effect.[2] The 2012 American College of Chest Physicians guidelines for antithrombotic therapy in neonates and children outline initiation of anticoagulant therapy with warfarin, unfractionated heparin, and low molecular weight heparin (LMWH). However, many of the dosage recommendations and the length of therapy are based on low-grade evidence.[3,4] Other considerations include route of administration, drug-drug interactions, and drug-dietary interactions.[4]

To effectively and safely manage patients on warfarin or heparin, many institutions have developed pharmacy-driven protocols for inpatients and outpatients, allowing trained pharmacists to work collaboratively with physicians in monitoring and adjusting anticoagulant dosages. These protocols guide clinical decision-making when selecting the most appropriate anticoagulant regimen. There are several clinical trials currently underway evaluating the safety and efficacy of direct oral anticoagulants (DOACS) in pediatrics, namely, rivaroxaban and apixaban. Guidelines for pediatric DOAC use have not yet been published. If clinicians decide to initiate DOAC therapy, the benefit must outweigh the risk. Until the results of studies or updated guidelines are published, institutions will continue to use standard anticoagulant treatment protocols specific to their patient population. This article reviews standard therapy and discusses information from the current ongoing clinical studies using the DOACs.

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