Introduction
Thromboembolic events in children with congenital or acquired heart
disease are a significant concern for pediatric cardiologists.
Thromboembolic event rates are elevated in this population due to a
multitude of factors including disruption of laminar blood flow,
endothelial disruption, presence of central venous catheters, surgical
introduction of foreign materials, iatrogenic and clinical
coagulopathies from hepatic congestion, and hypoperfusion in the setting
of abnormal cardiac function [1]. Unfortunately, a subset of these
patients progress towards the need for cardiac transplantation, with
continued needs for thromboembolic treatments and prophylaxis.
Traditionally, anticoagulation therapy has consisted of either low
molecular weight heparin (LMWH) or oral vitamin K antagonists (i.e.
warfarin). Guidelines have been established regarding the use of these
agents for prophylaxis in children with heart disease [2] and in
those awaiting heart transplantation [3]. However, these therapies
have their downsides. Warfarin requires frequent monitoring with serum
levels greatly affected by changes in diet, hepatic function and
interactions with other medications. LMWH requires twice-daily
subcutaneous injections, along with serum monitoring requiring
venipuncture, both of which are a challenge in the pediatric population.
Direct oral anticoagulants (DOACs), which include the direct thrombin
inhibitor dabigatran and factor Xa inhibitors (Apixaban, Rivaroxaban,
Edoxaban), have recently become the anticoagulants of choice in adults
with acquired non-valvar cardiac disease, such as atrial fibrillation
[4], left ventricular thrombus after myocardial infarction and
adults with congenital heart disease [5-7]. In pediatrics, DOACs are
increasingly being considered given the upside of less frequent
monitoring and oral administration [8], in addition to their
independence of antithrombin III and linear dose response [9].
Apixaban, a direct, reversible inhibitor of factor Xa, is of particular
interest in ongoing pediatric trials [10-11]. There is emerging
evidence in adults to suggest apixaban is more efficacious than
rivaroxaban, the only currently Food and Drug Administration (FDA)
approved factor Xa inhibitor in the pediatric population [12].
In this study, we describe our use of apixaban in children and young
adults awaiting heart transplantation, including outcomes related to
bleeding and thrombosis during wait-list and early post-transplant
periods.