In the United States, and globally, the “REDS” moniker is well-known and widely regarded in the transfusion medicine community. Funded by the US National Heart, Lung and Blood Institute of NIH, the original REDS program (initiated in 1989 and renewed through 2001) stood for Retrovirus Epidemiology Donor Study and was introduced to address concerns for HIV and other infectious risks in the blood supply. Successive iterations have broadened the scope of the program, combining systematic data collection, laboratory and survey research, judicious use of stored repository samples, and rapid response capacity for newly emerging agents such as Zika or SARS-CoV-2 viruses. The REDS-II program from 2004-2012 continued its focus on blood donors and infectious disease, but enlarged the research portfolio to include non-infectious blood safety issues such as HLA antibodies in blood donors and risk for transfusion related acute lung injury (TRALI) and donation safety issues such as risk for iron depletion in blood donors. REDS-III was a 7-year program (2011-2018) that expanded the number of partners and investigator expertise by adding 12 hospitals that sourced blood from the 4 participating blood centers. Inclusion of data from blood recipients supported analyses of the epidemiology of plasma transfusion, functional improvement following red cell transfusion in elderly patients, and correlates adverse events following transfusion.
The latest and ongoing incarnation of REDS, called REDS-IV-P, reflects the natural progression of NHLBI’s interest in improving donation and transfusion safety as well as outcomes. Maintaining the same acronym while adjusting the name to capture its emphasis on non-adult patients who receive blood components (Recipient Epidemiology and Donor Evaluation Study), REDS-IV-P continues many activities of REDS-III but expands the patient base beyond adults to neonataland pediatric patient populations. Begun in 2019 and funded for 7 years, REDS-IV-P will include as a key resource a vein-to-vein database allowing for statistical evaluation of donor-, manufacturing-, and patient-related factors that influence donation outcomes. While the importance of donor and patient characteristics is expected, examples of the manufacturing process that might alter component quality or potency include pathogen inactivation and gamma irradiation, especially if followed by prolonged storage.
The data are sourced from the program’s four domestic “hubs,” which like REDS-III consists of one or more blood centers partnered with at least one tertiary care hospital and one community hospital. The hubs are located in the Connecticut (Red Cross region), New York, Wisconsin, and California; as well as an international collaboration with Brazilian investigators, who had participated in REDS-III. Altogether, the REDS-IV-P program represents 22 hospitals (which includes 6 children’s hospitals). In addition, the program is to be supported by a central laboratory and a data coordinating center.
Aside from multiple data analyses leveraging linked donor-recipient variables, REDS-IV-P will also conduct stand-alone projects that are patient- and/or donor-facing. The TIPI Study (Transfusion in Preterm Infants), which is already underway, is designed to identify the donor, manufacturing, and patient factors that affect outcomes for very low birthweight (<1500 g) infants, about 50% of whom receive a blood transfusion.
The RBC Impact Study (RBC IMProving TrAnsfusions for Chronically Transfused Pediatric and Adult Recipients) focuses primarily on patients with sickle cell disease and thalassemia, populations that frequently receive red cell products as supportive therapy. The study will evaluate transfusion efficacy as a function of defined factors of both donor and recipient, as well as storage characteristics. These and several other epidemiological and laboratory studies are described in more detail in a recent Transfusion paper authored by Cassandra Josephson, et al.
Following the end of the REDS-IV-P program in 2026, much of the data from the database and from other studies will be deposited as public use datasets, in de-identified form, in the BioLincc database (https://www.biolincc.nhlbi.nih.gov/) for ongoing curation and availability as a resource to the transfusion medicine investigator community.
REDS-IV-P follows a strong legacy of contributions by REDS to blood safety and transfusion medicine, and the program is poised to continue this success with attention to understudied and underserved populations and to further the advancement of personalized medicine research. The REDS-IV-P program welcomes collaborations with outside investigators and interested parties should feel free to reach out to the author of this article or other co-authors of the Josephson paper.
- Red Cross Science Website: https://www.redcrossblood.org/biomedical-services/educational-resources/science.html
- REDS-IV-P Program Website: https://redsivp.com/
- Josephson CD, et al. The Recipient Epidemiology and Donor Evaluation Study-IV-Pediatric (REDS-IV-P): A research program striving to improve blood donor safety and optimize transfusion outcomes across the lifespan. Transfusion. 2022 May;62(5):982-999.
- Kleinman S, et al. The National Heart, Lung, and Blood Institute Recipient Epidemiology and Donor Evaluation Study (REDS-III): a research program striving to improve blood donor and transfusion recipient outcomes. Transfusion. 2014 Mar;54(3 Pt 2):942-55.
- Kleinman S, et al. The National Heart, Lung, and Blood Institute retrovirus epidemiology donor studies (Retrovirus Epidemiology Donor Study and Retrovirus Epidemiology Donor Study-II): twenty years of research to advance blood product safety and availability. Transfus Med Rev. 2012 Oct;26(4):281-304, 304.e1-2.