Red cell transfusion survival in sickle cell disease is reduced by donor characteristics and recipient spleen activity

Red blood cell (RBC) transfusion therapy in sickle cell disease (SCD) is used to treat and prevent disease complications by providing non-sickle erythrocytes that survive for weeks in circulation. Suppression of sickle hemoglobin between transfusion episodes is dependent on donor RBC survival. We present an observational clinical trial of transfusion survival in pediatric and adult patients with SCD receiving chronic transfusion therapy using biotin-labeling to measure donor RBC lifespan. For each transfusion episode, aliquots from 2-3 RBC units were separated from each unit, biotin-labeled at 2, 6, or 18 µg/mL, and transfused to the patient after the main RBC unit. Biotin-labeled RBCs (B-RBC) were analyzed by flow cytometry at 15-minutes, 24 hours, and weekly through 16 weeks post-transfusion. Recipient splenic volume was assessed by ultrasound. Glucose-6-phosphate dehydrogenase (G6PD) enzyme activity and hemoglobinopathy status were determined for each RBC unit. Twenty recipients received a total of 22 B-RBC transfusion episodes (49 units). Median post-transfusion recovery was 97.3% (79.4-112.7%) at 24-hours (PTR-24), 80% at 28 days (35-105%), and 21% (2-48%) at 90 days. Median time to 50% recovery (T50) was 60 days (23-85). In multivariate mixed effects analysis, recipient spleen volume and donor G6PD deficiency or alpha-thalassemia trait were associated with decreased B-RBC survival. Recipient RBC alloimmunization showed a non-significant association with decreased RBC survival in multivariate analysis. Donor and recipient characteristics that reduce RBC survival have the potential to impact transfusion effectiveness and SCD management and require future studies in larger cohorts. NCT04426591.