The Presence and Percentage of Circulating Nucleated Red Blood Cells Reveal Distinct Characteristics in Adults With Sickle Cell Disease
Abstract
Although circulating nucleated red blood cells (cNRBCs) have previously been detected in patients with sickle cell disease (SCD), their prevalence and clinical significance during steady‐state disease have not been established. We retrospectively analyzed 270 adults with an SS or Sβ 0 ‐thalassemia genotype. cNRBCs were counted during steady‐state disease. Patients were classified as high cNRBC+ (> 3 per 100 white blood cells (WBCs)), low cNRBC+ (1–3 per 100 WBCs), or cNRBC− (no cNRBCs). cNRBC+ and cNRBC− patients were compared with regard to clinical and laboratory data and in vitro erythroid differentiation from peripheral blood CD34+ cells. cNRBCs were detected in 65.6% of the patients and encompassed all terminal erythroid stages. High cNRBC+ patients were more likely to be receiving hydroxyurea ( p = 0.024). cNRBC+ patients exhibited a lower median [IQR] hemoglobin level (8.8 [7.8–10] and 8.4 [7.4–9.4] in the high and low cNRBC+ groups, respectively vs. 9.3 [8.3–9.9] g/dL in the cNRBC− group; p = 0.024). The cNRBC+ percentage was correlated negatively with the reticulocyte and WBC counts and positively with the mean corpuscular volume and the ferritin level. Clinically, a trend toward a greater likelihood of acute chest syndrome was observed in cNRBC+ patients. High cNRBC+ patients' cells exhibited accelerated erythroid differentiation in vitro, suggestive of dyserythropoiesis. cNRBCs constitute a common, easily measurable marker of a distinct hematological phenotype in adult patients with SCD: more severe anemia and signs of dyserythropoiesis. Prospective studies are needed to determine the value of the cNRBC percentage for predicting disease severity and guiding the treatment of dyserythropoiesis.
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BibTeX
@article{boccadifuoco2026presence,
title = {{The Presence and Percentage of Circulating Nucleated Red Blood Cells Reveal Distinct Characteristics in Adults With Sickle Cell Disease}},
author = {Ugo Boccadifuoco and Ivan Lerner and Auria Godard and Luc Darnige and Laure Joseph and Wassim El Nemer and Geoffrey Cheminet and Jean‐benoit Arlet},
journal = {American Journal of Hematology},
year = {2026},
month = sep,
doi = {10.1002/ajh.70497},
url = {https://hal.science/hal-05756921v1},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - The Presence and Percentage of Circulating Nucleated Red Blood Cells Reveal Distinct Characteristics in Adults With Sickle Cell Disease
AU - Ugo Boccadifuoco
AU - Ivan Lerner
AU - Auria Godard
AU - Luc Darnige
AU - Laure Joseph
AU - Wassim El Nemer
AU - Geoffrey Cheminet
AU - Jean‐benoit Arlet
PY - 2026
DA - 2026/09/09
JO - American Journal of Hematology
DO - 10.1002/ajh.70497
UR - https://hal.science/hal-05756921v1
AB - Although circulating nucleated red blood cells (cNRBCs) have previously been detected in patients with sickle cell disease (SCD), their prevalence and clinical significance during steady‐state disease have not been established. We retrospectively analyzed 270 adults with an SS or Sβ 0 ‐thalassemia genotype. cNRBCs were counted during steady‐state disease. Patients were classified as high cNRBC+ (> 3 per 100 white blood cells (WBCs)), low cNRBC+ (1–3 per 100 WBCs), or cNRBC− (no cNRBCs). cNRBC+ and cNRBC− patients were compared with regard to clinical and laboratory data and in vitro erythroid differentiation from peripheral blood CD34+ cells. cNRBCs were detected in 65.6% of the patients and encompassed all terminal erythroid stages. High cNRBC+ patients were more likely to be receiving hydroxyurea ( p = 0.024). cNRBC+ patients exhibited a lower median [IQR] hemoglobin level (8.8 [7.8–10] and 8.4 [7.4–9.4] in the high and low cNRBC+ groups, respectively vs. 9.3 [8.3–9.9] g/dL in the cNRBC− group; p = 0.024). The cNRBC+ percentage was correlated negatively with the reticulocyte and WBC counts and positively with the mean corpuscular volume and the ferritin level. Clinically, a trend toward a greater likelihood of acute chest syndrome was observed in cNRBC+ patients. High cNRBC+ patients' cells exhibited accelerated erythroid differentiation in vitro, suggestive of dyserythropoiesis. cNRBCs constitute a common, easily measurable marker of a distinct hematological phenotype in adult patients with SCD: more severe anemia and signs of dyserythropoiesis. Prospective studies are needed to determine the value of the cNRBC percentage for predicting disease severity and guiding the treatment of dyserythropoiesis.
SN - 0361-8609
SN - 1096-8652
ER -