# Kinetics of Red Blood Cell Clearance in Chronically Transfused Children with Sickle Cell Disease

> **NIH NIH K23** · EMORY UNIVERSITY · 2022 · $169,695

## Abstract

Project Summary
Sickle cell disease (SCD) carries significant morbidity as a result of red blood cell (RBC) sickling and
hemolysis. Stroke is one of the most devastating sequelae of SCD. Chronic transfusion therapy (CTT) reduces
stroke risk by (1) supplying normal, non-sickle RBC to circulation, thereby reducing the percentage of
endogenous sickle RBC in circulation, and (2) maintaining a higher hemoglobin (Hb), thereby suppressing
erythropoiesis of new sickle RBC. While the efficacy of CTT in stroke prophylaxis is well-established, nearly
45% of children continue to have silent or overt strokes despite CTT. The failure of CTT to prevent stroke
events may be related to inadequate reduction of circulating sickle RBC and erythropoiesis. The amount of
circulating sickle-RBC is related to the survival kinetics of both transfused RBC and endogenous sickle RBC. In
a large, longitudinal analysis of CTT in SCD, we found wide variation in the survival of donor RBC following
transfusion, with faster clearance associated with patient immune features (historical RBC alloimmunization
and spleen presence) and with donor RBC glucose-6-phosphate-dehydrogenase (G6PD) deficiency. To better
understand the roles of patient and donor factors in the survival and clearance of transfused RBC, we propose
a mechanistic, clinical trial during chronic transfusion episodes in patients with SCD, in which a small aliquot of
each transfused unit is labeled with biotin conjugated to RBC surface proteins, to safely identify and measure
the in vivo survival of donor RBC. Aim 1 will examine the relationships of the recipient’s immune system (past
alloimmunization, splenic volume, and markers of reticuloendothelial system function) on the post-transfusion
survival of biotin-labeled donor RBC. Aim 2 will examine the relationships of donor RBC G6PD levels and
donor RBC metabolomics with the in vivo survival and changes in donor RBC senescence markers.
Completion of these aims will increase our understanding of mechanisms for the variability in RBC survival
during CTT, identifying donor and recipient risk factors for decreased RBC survival. Ultimately this knowledge
will inform the management of CTT to improve the prevention of strokes in SCD. The applicant, Dr. Yee, is a
pediatric hematologist and an emerging clinical researcher in SCD, with a master’s degree in clinical research
and experience with pilot and prospective studies of patient-oriented research in SCD. Dr. Yee has identified
an exceptional mentorship team with expertise in RBC survival studies and biotinylation, donor RBC
metabolomics, and clinical research in SCD. The candidate's short-term career goals for this K23 application
are to 1) Develop formal expertise in transfusion medicine; 2) Expand expertise in conducting prospective,
interventional clinical research in pediatric SCD and transfusion medicine; 3) Learn the use and interpretation
of biotinylation of RBC transfusion to study transfusion survival in vivo. The ...

## Key facts

- **NIH application ID:** 10401778
- **Project number:** 5K23HL146904-03
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Marianne Elaine McPherson Yee
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $169,695
- **Award type:** 5
- **Project period:** 2020-05-03 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10401778

## Citation

> US National Institutes of Health, RePORTER application 10401778, Kinetics of Red Blood Cell Clearance in Chronically Transfused Children with Sickle Cell Disease (5K23HL146904-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10401778. Licensed CC0.

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