Causes of red blood cell loss during extracorporeal membrane oxygenation

Abstract

Background: Pediatric patients on extracorporeal membrane oxygenation (ECMO) often receive repeated red blood cell (RBC) transfusions. This study aims to quantify and characterize causes of RBC loss on ECMO. Methods: This retrospective, single-center, observational study includes 91 ECMO patients (age 1 day-20 years). An RBC loss index (RLI), equal to ml RBCs lost per liter of patient + circuit volume per hour, was calculated from the changes in hematocrit and transfused RBCs. To measure the contribution of RBC injury/activation, RBC extracellular vesicle (REV) generation was measured by flow cytometry. Results: Median RLI on ECMO was 1.9 ml/L/h, 13-fold higher than normal RBC production rate (0.15 ml/L/h) and equivalent to a 4.6 drop in hematocrit/day. Median RBC loss was higher in patients who died (2.95 ml/L/h) versus survived (1.70 ml/L/h, p = .0008). RLI correlated with transfusion rate (r(2) = 0.71); however, transfusion rate (ml/kg) underestimated RBC loss in patients with large changes in hematocrit and over-estimated RBC loss in neonates where the circuit volume is greater than the patient blood volume. In non-bleeding patients, intravascular hemolysis represented 16% of total RBC loss and diagnostic phlebotomy 24%, suggesting that similar to 60% of RBC loss was due to other causes. REV generation was increased sevenfold to ninefold during ECMO. Discussion: RLI (ml/L/h) is a more reliable quantitative indicator of RBC loss than transfusion rate (ml/kg) for pediatric patients on ECMO. Phlebotomy and intravascular hemolysis only account for 40% of RBC loss in non-bleeding ECMO patients. High REV generation suggests sublethal damage and extravascular clearance may be a cause of RBC loss on ECMO.