Antithrombin Levels and Heparin Responsiveness during Venoarterial Extracorporeal Membrane Oxygenation: A Prospective Single-center Cohort Study

Abstract

Background Unfractionated heparin, administered during veno-arterial extracorporeal membrane oxygenation to prevent thromboembolic events, largely depend on plasma antithrombin for its antithrombotic effects. Decreased heparin responsiveness seems frequent on extracorporeal membrane oxygenation however its association with acquired antithrombin deficiency is poorly understood. Our objective was to describe longitudinal changes in plasma antithrombin levels during extracorporeal membrane oxygenation support and evaluate the association between antithrombin levels and heparin responsiveness. We hypothesized that extracorporeal membrane oxygenation support would be associated with acquired antithrombin deficiency and related decreased heparin responsiveness. Methods Adults receiving veno-arterial extracorporeal membrane oxygenation were prospectively included. All patients received continuous intravenous unfractionated heparin using a standardized protocol (target anti-Xa 0.3-0.5 IU.mL -1). For each patient, arterial blood was withdrawn into citrate-containing tubes, at 11 time-points (from H0 up to day 7) . Anti-Xa (without dextran or antithrombin added) and antithrombin levels were measured. The primary outcome was antithrombin plasma level. In the absence of consensus, antithrombin deficiency was defined as a time-weighted average of antithrombin ≤70%. Data regarding clinical management and heparin dosage were collected. Results Fifty patients, including 42% post-cardiotomy, were included between April 2020 and May 2021, with a total of 447 samples. Median extracorporeal membrane oxygenation duration was 7 (interquartile range, 4-12) days. Median antithrombin level was 48 (37-60)% at H0. Antithrombin levels significantly increased throughout the follow-up. Time-weighted average of antithrombin levels was 63 (57-73)%, and was ≤70% in 32 (64%) of patients. Overall, 45 (90%) patients had at least one antithrombin value below 70%, and 35 (70%) below 50%. Antithrombin levels were not significantly associated with heparin responsiveness evaluated by anti-Xa assay or heparin dosage. Conclusions Veno-arterial extracorporeal membrane oxygenation support was associated with a moderate acquired antithrombin deficiency, mainly during the first 72 hours, that did not correlate with heparin responsiveness.