Red cell physiologic stress results in lower quality transfusions: a randomized trial in adults with sickle cell disease.

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. This 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 adult patients (aged >16 years) with SCD; 13 participants were randomized to each study arm, that is, 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 patients receiving units with higher surface-exposed PS and PE, regardless of storage age, had a reduced hemoglobin (Hb) increment at 2 weeks (PS-PE high, 0.59 g/dL; PS-PE low, 1.04 g/dL; P = .04), increased pain crises (incidence rate ratio, 7.44; 95% confidence interval [CI], 1.53-36.25), and higher odds of reported illness (odds ratio, 1.94; 95% CI, 1.06-3.54). Furthermore, posttransfusion serum iron predicted subsequent subjective symptoms of illness (receiver operating characteristic-area under the curve, 0.76) and correlated with smaller increases in HbA percent after transfusion (r =-0.36; P = .04). These data suggest that the physiologic state of transfused red cells 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. This trial was registered at www.clinicaltrials.gov as #NCT03704922.