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Updated: Apr 6, 2026

A Precision Medicine Tool for Measurement and Monitoring of Hemoglobin S in Sickle Cell Disease Patients Receiving Transfusion Therapy
Integration of red cell genotyping into the blood supply chain: a population-based study
Background:
When problems with compatibility arise, transfusion services often use time-consuming serological tests to identify antigen-negative red cell units for safe transfusion. New methods have made red cell genotyping possible for all clinically relevant blood group antigens. We did mass-scale genotyping of donor blood and provided hospitals with access to a large red cell database to meet the demand for antigen-negative red cell units beyond ABO and Rh blood typing.
Methods:
We established a red cell genotype database at the BloodCenter of Wisconsin on July 17, 2010. All self-declared African American, Asian, Hispanic, and Native American blood donors were eligible irrespective of their ABO and Rh type or history of donation. Additionally, blood donors who were groups O, A, and B, irrespective of their Rh phenotype, were eligible for inclusion only if they had a history of at least three donations in the previous 3 years, with one donation in the previous 12 months at the BloodCenter of Wisconsin. We did red cell genotyping with a nanofluidic microarray system, using 32 single nucleotide polymorphisms to predict 42 blood group antigens. An additional 14 antigens were identified via serological phenotype. We monitored the ability of the red cell genotype database to meet demand for compatible blood during 3 years. In addition to the central database at the BloodCenter of Wisconsin, we gave seven hospitals online access to a web-based antigen query portal on May 1, 2013, to help them to locate antigen-negative red cell units in their own inventories.
Findings:
We analysed genotype data for 43,066 blood donors. Requests were filled for 5661 (99.8%) of 5672 patient encounters in which antigen-negative red cell units were needed. Red cell genotyping met the demand for antigen-negative blood in 5339 (94.1%) of 5672 patient encounters, and the remaining 333 (5.9%) requests were filled by use of serological data. Using the 42 antigens represented in our red cell genotype database, we were able to fill 14,357 (94.8%) of 15,140 requests for antigen-negative red cell units from hospitals served by the BloodCenter of Wisconsin. In the pilot phase, the seven hospitals identified 71 units from 52 antigen-negative red cell unit requests.
Interpretation:
Red cell genotyping has the potential to transform the way antigen-negative red cell units are provided. An antigen query portal could reduce the need for transportation of blood and serological screening. If this wealth of genotype data can be made easily accessible online, it will help with the supply of affordable antigen-negative red cell units to ensure patient safety.
Funding:
BloodCenter of Wisconsin Diagnostic Laboratories Strategic Initiative and the NIH Clinical Center Intramural Research Program.
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