Materials and Methods
Our study is a retrospective, single-center analysis of all patients who
received apixaban while listed for cardiac transplantation at Boston
Children’s Hospital. Data was obtained from review of the electronic
medical record upon approval by the Boston Children’s institutional
review board (IRB-P00037911). This study was performed in line with the
principles of the Declaration of Helsinki. No patients meeting this
criteria were excluded from the study. Data collected included patient
demographics, pertinent medical history and baseline laboratory results.
Apixaban dosing was weight-based with dose adjustment to the nearest
0.625mg BID (1/4 of a 2.5mg pill) based on available formulation.
Apixaban serum levels were obtained using drug-specific anti-Xa
chromogenic STA® Liquid Anti-Xa with apixaban Calibrator and Controls
(Diagnostica Stago Inc, Asnieres-sur-Seine, France) [13] with
reportable range of <23ng/ml - 500ng/ml. analysis. Goal
apixaban levels were extrapolated from adult studies [14, 15] and
center experience: standard risk prophylaxis 80-150ng/mL, standard risk
prophylaxis or treatment of thrombosis 100-300ng/mL and high-risk
prophylaxis (i.e. ventricular assist devices (VAD) or Kawasaki with
giant coronary aneurysm) 200-300ng/mL. Prior to the availability of
apixaban level testing, low molecular weight heparin anti-Xa levels were
followed with goal therapeutic level of greater than 1.5 units/mL and a
maximum level reported of the assay of 2.0 units/ml.
Our institutional protocol included holding apixaban upon notification
of organ acceptance. Arrival to the operating room (OR) was determined
as documented in the anesthesia record. Significant bleeding was defined
by one of four criteria: an average chest tube output upon arrival to
the cardiac intensive care unit (CICU) of> 10mL/kg/hour for the first 2 hours,> 5mL/kg/hour over the first 4 hours, need for
surgical re-exploration due to complications from bleeding, or clinical
diagnosis of cardiac tamponade. Medians were calculated for all
continuous variables with 25th and
75th percent quartiles reported.