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

ABSTRACT: Red blood cell (RBC) transfusion therapy in sickle cell disease (SCD) is used to treat and prevent disease complications by providing nonsickle erythrocytes that survive for weeks in circulation. The 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 life span. For each transfusion episode, aliquots from 2 to 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 after 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 posttransfusion recovery was 97.3% (range, 79.4%-112.7%) at 24 hours, 80% (range, 35%-105%) at 28 days, and 21% (range, 2%-48%) at 90 days. Median time to 50% recovery was 60 days (23-85 days). In multivariate mixed-effects analysis, recipient spleen volume and donor G6PD deficiency or α-thalassemia trait were associated with decreased B-RBC survival. Recipient RBC alloimmunization showed a nonsignificant association with decreased RBC survival in multivariate analysis. Donor and recipient characteristics that reduce RBC survival have the potential to affect transfusion effectiveness and SCD management and require future studies in larger cohorts. This trial was registered at www.clinicaltrials.gov as #NCT04426591.