Related Experiment Video
Updated: Apr 3, 2026
A Precision Medicine Tool for Measurement and Monitoring of Hemoglobin S in Sickle Cell Disease Patients Receiving Transfusion Therapy
Absolute Reticulocyte Count Acts as a Surrogate for Fetal Hemoglobin in Infants and Children with Sickle Cell Anemia
Emily Riehm Meier1, Colleen Byrnes2, Maxine Weissman3
1Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, United States of America; Center for Cancer and Blood Disorders, Children's National Medical Center, Washington, D.C., United States of America; Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, D.C., United States of America.
Insights
In children with sickle cell anemia (SCA), a higher absolute reticulocyte count (ARC) is linked to lower fetal hemoglobin (HbF) levels. This finding supports using ARC as a biomarker for SCA severity in pediatric patients.
Area of Science:
- Hematology
- Pediatric Medicine
- Genetics
Background:
- Hemoglobin switching, the transition from fetal hemoglobin (HbF) to adult hemoglobin (HbS), is typically complete by six months in humans.
- In sickle cell anemia (SCA), infants experience reticulocytosis as HbF is replaced by HbS, impacting disease progression.
- Understanding factors influencing HbF levels is crucial for managing SCA severity in children.
Purpose of the Study:
- To investigate the relationship between absolute reticulocyte count (ARC) and fetal hemoglobin (HbF) levels in pediatric SCA patients.
- To assess the utility of ARC as a potential biomarker for SCA severity in children.
Main Methods:
- An observational study involving 106 pediatric SCA patients (1 month to 20 years) not on hydroxyurea or transfusions.
- Measurement of hematologic data, including ARC and HbF levels, at steady state.
- Enumeration of F-cells using flow cytometry and comparison between infants with ARC ≥ 200 K/μL and ARC < 200 K/μL.
Main Results:
- Mean HbF and F-cell levels were significantly lower in pediatric SCA patients with ARC ≥ 200 K/μL compared to those with ARC < 200 K/μL.
- A negative correlation between HbF/F-cell percentages and ARC was observed in infants and children aged 1-9 years.
- This inverse relationship between HbF and ARC was not significant in patients older than 10 years.
Conclusions:
- Decreased HbF expression and distribution in childhood SCA correlates with increased reticulocyte production.
- Absolute reticulocyte count (ARC) serves as a valuable disease severity biomarker in pediatric sickle cell anemia.
- These findings support the clinical utility of reticulocyte enumeration for assessing SCA severity in children.
Abstract:
Hemoglobin switching is largely complete in humans by six months of age. Among infants with sickle cell anemia (HbSS, SCA), reticulocytosis begins early in life as fetal hemoglobin (HbF) is replaced by sickle hemoglobin (HbS). The objective of this study was to determine if absolute reticulocyte count (ARC) is related to HbF levels in a cohort of pediatric SCA patients. A convenience sample of 106 children with SCA between the ages of 1 month and 20 years who were not receiving hydroxyurea or monthly blood transfusions were enrolled in this observational study. Hematologic data, including ARC and HbF levels, were measured at steady state. F-cells were enumerated by flow cytometry. Initial studies compared infants with ARC greater than or equal to 200 K/μL (ARC ≥ 200) based upon the previously reported utility of this threshold as a predictive marker for SCA severity. Mean HbF and F-cell levels were significantly lower in the ARC ≥ 200 group when compared to the ARC < 200 group. Both HbF and F-cell percentages were negatively correlated to ARC in infants and in children between the ages of 1 and 9 years. However, the inverse relationship was lost after the age of 10 years. Overall, decreased expression and distribution of HbF during childhood SCA is well-correlated with increased reticulocyte production and release into the peripheral blood. As such, these data further support the clinical use of reticulocyte enumeration as a disease severity biomarker for childhood sickle cell anemia.
