Donor Red Blood Cell Survival in Recipients with Sickle Cell Disease

About This Grant

Project Summary Red blood cell (RBC) transfusion is an essential part of the management of sickle cell disease (SCD). The effectiveness of transfusion therapy to treat acute disease complications and prevent chronic disease progression have unique considerations in SCD that are dependent upon post-transfusion RBC survival. For many individuals with SCD who receive acute or chronic transfusions, transfusion survival and thus effectiveness is suboptimal. The NHLBI State of the Science in Transfusion Medicine symposium identified optimization of RBC transfusion outcomes for recipients with SCD as a key clinical and research priority. The proposed research will evaluate the impact of donor and recipient factors on the survival of transfused RBCs in recipients with SCD and will examine mechanisms contributing to RBC clearance in both the recipient and the donor. Based on our preliminary data, we hypothesize that RBC components from donors with G6PD deficiency or with alpha-thalassemia trait will have decreased post-transfusion in vivo survival as compared to normal donor RBCs. We have previously demonstrated that recipients with SCD have a much higher likelihood of receiving transfusion from donors with these RBC conditions that are common among healthy donors with African ancestry. We additionally hypothesize that recipients with past RBC alloimmunization responses will have faster clearance of transfused RBCs via mechanisms of spleen and hepatic phagocytic activity. We propose an experimental, interventional, controlled trial with a paired study design that will allow recipient and donor factors to be assessed independently without confounding. Through large-scale next generation sequencing (NGS) genetic screening of at least 10,000 African American blood donors through LifeSouth Community Blood Centers, we will create a database of eligible blood donors including blood type, RBC minor antigen genotype for matching to recipients, G6PD, and alpha-thalassemia hemoglobinopathy status. Pairs of minor antigen-similar blood donors (G6PD deficiency to normal, and alpha-thalassemia to normal) will be recruited for donation, with transfusion directed to pairs of recipients with SCD (alloimmunized vs. non- alloimmunized). Biotin-labeling will be used to measure post-transfusion RBC survival kinetics. Our aims are to (1) determine differences in post-transfusion survival for RBC components from donors with and without G6PD deficiency or alpha-thalassemia trait, and (2) to determine differences in the clearance of transfused RBCs in recipients with SCD with and without past alloimmunization. We will conduct the project through the Georgia Comprehensive Sickle Cell Center at Emory University-affiliated Grady Memorial Hospital. Our project has the potential to improve the management of RBC transfusion therapy, with focus on tangible areas such as donor screening and selection, and identification of recipients at increased risk of suboptimal transfusion survival and efficacy.