Antithrombin Dose Optimization in Extracorporeal Membrane Oxygenation in Infants

Abstract

Anticoagulation in extracorporeal membrane oxygenation (ECMO) is challenging, with significant morbidity and mortality associated with thrombotic complications. Unfractionated heparin (UFH) is commonly used, which depends on native antithrombin (AT) function to exert anticoagulant effects. Antithrombin deficiency is common in infants on ECMO and replacement with AT concentrate may be warranted. However, dosing recommendations in this population are limited. We conducted a retrospective review of patients <1 year of age who received recombinant AT (ATryn) while on UFH and ECMO between January 1, 2010 and December 31, 2017. Commonly used dosing equations were assessed to determine their ability to predict postdose AT levels. Patient AT levels were compared with equation-predicted postdose AT levels to determine a correlation. A total of 102 doses in 41 patients were used for analysis. Baseline mean AT level was 43% (±13%) and mean AT doses were 134 units (±58.1 units) or 40.5 units/kg (±18.7 units/kg). Median increase in the AT level was 8% (interquartile range 2-17%) with a mean postdose level of 52.6% (±14.2%). Weight-based dosing poorly correlated with postdose AT levels (r 2 = 0.082). Postdose levels were best predicted when using an equation that included desired change in the AT level from baseline, the patient's weight, and added weight from the volume of the ECMO circuit (r 2 = 0.427). Prospective studies are needed to evaluate optimal dosing strategies, safety, and efficacy of AT in this population.

Recommendations on Monitoring and Replacement of Antithrombin, Fibrinogen, and Von Willebrand Factor in Pediatric Patients on Extracorporeal Membrane Oxygenation: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference

“…Summary of evidence. Nineteen studies reporting on AT use were included in the analysis (24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42). The major themes that emerged from these studies include: 1) AT activities were low at initiation of ECMO; 2) AT activity increased after AT administration but the dose response was variable; 3) the association between AT administration and heparin dose rate and coagulation monitoring parameters was mixed but most studies showed no association; and 4) association between AT and clinical outcomes was mixed.…”

Extracorporeal Anticoagulation With Bivalirudin; Is the Best Still to Come?

“…We read with great interest the Brief Communication by Seelhammer et al in response to our manuscript “Antithrombin Dose Optimization in Extracorporeal Membrane Oxygenation in Infants”. 1 The authors write in support of direct Thrombin inhibitors (DTI) as alternatives to unfractionated heparin (UFH) for the systemic anticoagulation of patients supported by extracorporeal membrane oxygenation (ECMO). Because anticoagulation with UFH requires a multitude of laboratory tests and sufficient levels of the cofactor antithrombin for effect, they suggest the time may be right for DTIs to replace UFH as the first line anticoagulant for adult and pediatric patients supported on ECMO.…”

Antithrombin Replacement and Extracorporeal Membrane Oxygenation: The time is ripe for a Simpler Solution

“…1 With this in mind, we read with great interest the salient study by Liviskie et al investigating the effectiveness of AT dosing equations to predict postdose AT levels in a cohort of 41 pediatric patients under 1 year of age. 2 Important findings included a low baseline mean AT level of 43% (±13%) and mean postdose AT level of 52.6% (±14.2%) with poor correlation using weight-based dosing equations (R 2 = 0.082) that improved with integration of desired change in AT level from baseline augmented with adjustments of the patients' weight supplemented with an adaptation utilizing the estimated weight from the volume of the ECMO circuit (R 2 = 0.427). We applaud the authors for providing highly granular detail on AT dosing on a relatively large number of infant ECMO patients along with the concurrent analysis leveraging a robust quantity of prediction equations that included commonly accepted as well as manufacturer recommended and institutional adjusted calculations.…”