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.