Red cell physiologic stress result in lower quality transfusions: A randomized trial in adults with sickle cell disease. Open Access

1. Donor variability is high regarding markers of physiologic stress and cannot be predicted by chronological storage age alone.

2. Patient serum iron and transfusion of PS-PE high red cell units were predictive of important clinical outcomes for adults with SCD.

People with sickle cell disease (SCD) may be transfused with red cell units that are near the end of their storage life, exposing them to components of the red cell storage lesion. The current study evaluated the clinical impact of storage age and red cell distress markers on chronically transfused adults with SCD. This randomized prospective clinical trial recruited 26 chronically transfused adults (>16-years-old) with SCD; 13 subjects were randomized to each study arm, i.e. targeted to receive only ≥ 30 day or ≤ 10 day stored red cell units for 3 consecutive outpatient transfusion events. The red cell units were evaluated via quantification of surface exposure of phosphatidylserine (PS) and phosphatidylethanolamine (PE). Differences in key clinical variables were also evaluated. We show that subjects receiving units with higher surface-exposed PS and PE, regardless of storage age, had a reduced hemoglobin increment at 2 weeks (PS-PE high: 0.59g/dL; PS-PE-low: 1.04g/dL, p=0.04), increased pain crises (IRR= 7.44; 95%CI: 1.53-36.25), and had higher odds of reported illness (OR=1.94; 95%CI: 1.06-3.54). Further, post-transfusion serum iron predicted subsequent subjective symptoms of illness (ROC-AUC=0.76) and correlated with smaller increases in HbA% post-transfusion (r=-0.36, p=0.04). These data suggest that, in addition to chronological storage age, the physiological state of transfused red cells as defined by PS and PE and subject serum iron may deleteriously affect patient outcomes. Future studies focusing on identifying and then avoiding lower quality red cell units in high-risk patients with SCD could enhance patient safety (NCT03704922).