# Donor and unit factors associated with recipient RBC alloimmunization formation

> **NIH NIH R21** · YALE UNIVERSITY · 2022 · $125,625

## Abstract

Red blood cell (RBC) alloimmunization is a leading cause of morbidity and mortality in transfusion and
pregnancy settings, resulting in hemolytic reactions and other adverse sequelae. Alloimmunization occurs in
up to 40% of some patient populations, including those with sickle cell disease (SCD); rates in patients with
myelodysplastic syndrome, thalassemia major, and autoimmunity are also high. Most studies of RBC
alloimmunization to date have focused on incidence/prevalence rates and recipient characteristics/diagnoses,
and few studies have evaluated blood donor or blood unit contributions to RBC alloantibody formation.
The National Heart, Lung, and Blood Institute (NHBLI) funded REDS-III vein-to-vein data set, available for
public use through BioLINCC, allows a unique opportunity to evaluate RBC alloantibodies in diverse recipients
across multiple institutions and to investigate potential blood donor and unit variables involved in transfusion
associated alloantibody formation. This data set contains inpatient and outpatient electronic health
information from four major blood centers and 12 community and academic hospitals in the United States, over
a 4-year time-period from 2013-2017. A query of the data set has shown that there are 651 subjects with a new
RBC antibody formed in the time interval (15 days to 16 weeks) following transfusion over which most
antibodies would be expected to form. The innovation of the current proposal lies in the unique ability to link
blood donor and blood unit characteristics to the recipient outcome of alloimmunization following RBC
transfusion.
Murine studies have shown that more rapid RBC clearance following transfusion is associated with a higher
degree of RBC alloimmunization, regardless of whether that increased clearance is due to longer storage
duration or other causes. As such, we hypothesize that factors associated with poorer RBC storage in
humans, including red cell storage duration, donor sex, or irradiation, will impact the likelihood of alloantibody
formation. We propose to complete a case: control (1:4) study, matching cases and controls for age, sex,
diagnosis, race, and ethnicity. With this study design, we propose: Aim 1) To investigate blood donor
characteristics associated with RBC alloimmunization in transfusion recipients and Aim 2) To investigate RBC
unit characteristics associated with RBC alloimmunization in transfusion recipients.
Long term, any blood donor or RBC unit characteristic associated with alloimmunization could be modified for
RBC units intended for patients at highest risk of RBC alloimmunization. If new antibody formation could be
minimized, transfusion safety will increase.

## Key facts

- **NIH application ID:** 10515205
- **Project number:** 1R21HL165306-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Ronald G. Hauser
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $125,625
- **Award type:** 1
- **Project period:** 2022-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10515205

## Citation

> US National Institutes of Health, RePORTER application 10515205, Donor and unit factors associated with recipient RBC alloimmunization formation (1R21HL165306-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10515205. Licensed CC0.

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