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.