Novel oxygenscan parameters differentiate unique hemolytic and inflammatory profiles associated with sickle cell disease genotypes

Sickle cell disease (SCD) is caused by hemoglobin S, which alters red blood cells (RBCs) rheological properties leading to vaso-occlusion and chronic hemolysis, the main hallmarks of the disease. They drive the broad clinical spectrum of SCD, including acute complications and progressive organ damage. Oxygen gradient ektacytometry (oxygenscan) is a functional assay that measures RBC deformability and sickling tendency during an oxygen gradient. Clinical validation of oxygenscan has been limited to a few studies with modest sample sizes and inconclusive results. To address these limitations, we assessed in the SCD cohort of 679 patients, two novel oxygenscan parameters: Slope measures how rapidly RBCs sickle during deoxygenation and EI20 measures RBC deformability at a fixed pO 2 , enabling a more detailed characterization of RBC behavior. Using linear and logistic regression analysis, we demonstrate that oxygenscan parameters distinguish SCD genotypes and hydroxyurea efficacy, underscoring their potential utility in phenotype characterization and clinical evaluation. Additionally, HbSβ 0 patients are often grouped with HbSS patients due to the comparable clinical phenotype, but our results suggest less severe sickling behavior and more pronounced association with inflammation in HbSβ 0 , while HbSS patients exhibited different hemolytic profile correlated with oxygenscan parameters. We further confirm that oxygenscan parameters are associated with hydroxyurea treatment status. These results support the biological relevance of oxygenscan parameters and emphasize that longitudinal and advanced machine learning approaches are required to fully capture the SCD complexity.

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Journal
Scientific Reports
Published
2026-08-03
DOI
https://doi.org/10.1038/s41598-026-62787-7
Primary Topic
Hemoglobinopathies and Related Disorders
Type
article
Field-Weighted Citation Impact
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article

Novel oxygenscan parameters differentiate unique hemolytic and inflammatory profiles associated with sickle cell disease genotypes

Emmanuelle Bourdelier, Cesare Rollo, Santiago Zazo, Tiziana Sanavia et al.
Scientific Reports
Hemoglobinopathies and Related Disorders
article

Novel oxygenscan parameters differentiate unique hemolytic and inflammatory profiles associated with sickle cell disease genotypes

Emmanuelle Bourdelier, Cesare Rollo, Santiago Zazo, Tiziana Sanavia, Marta García Bernal, Maria Paola Boaro, Sigrid van der Veen, Anna Collado Gimbert, Slimane Allali, María Teresa Coll Sibina, Marissa J.M. Traets, K. Fijnvandraat, Patricia A. Apellániz, Pablo Bartolucci, Mickaël Marin, Federico Álvarez, Juan Parras, Minke A.E. Rab, Piero Fariselli, David Benéitez, Elisabetta Mezzalira, Anita W. Rijneveld, Richard van Wijk, Caroline Le Van Kim, Amira Idrizovic, Raffaella Colombatti, Anna Ruiz‐Llobet, Aida Kidane, María del Mar Mañú‐Pereira, Montserrat Torrent, Griselda Vallès-Cardona, Eduard J. van Beers, Betzabel Cajiao Garcia, Ricard López, Nicolas Hebert, Bart J. Biemond, Emmanuel Adu, Saskia EM Schols, Marjon H. Cnossen, Erfan Nur, Mariane De Montalembert, Sara Reidel, Mirco D’Agnolo, Anne-Laure Pham Hung D’Alexandry D’Orengiani, Anabel Irina Rodríguez Pebé
article en

Abstract

Sickle cell disease (SCD) is caused by hemoglobin S, which alters red blood cells (RBCs) rheological properties leading to vaso-occlusion and chronic hemolysis, the main hallmarks of the disease. They drive the broad clinical spectrum of SCD, including acute complications and progressive organ damage. Oxygen gradient ektacytometry (oxygenscan) is a functional assay that measures RBC deformability and sickling tendency during an oxygen gradient. Clinical validation of oxygenscan has been limited to a few studies with modest sample sizes and inconclusive results. To address these limitations, we assessed in the SCD cohort of 679 patients, two novel oxygenscan parameters: Slope measures how rapidly RBCs sickle during deoxygenation and EI20 measures RBC deformability at a fixed pO 2 , enabling a more detailed characterization of RBC behavior. Using linear and logistic regression analysis, we demonstrate that oxygenscan parameters distinguish SCD genotypes and hydroxyurea efficacy, underscoring their potential utility in phenotype characterization and clinical evaluation. Additionally, HbSβ 0 patients are often grouped with HbSS patients due to the comparable clinical phenotype, but our results suggest less severe sickling behavior and more pronounced association with inflammation in HbSβ 0 , while HbSS patients exhibited different hemolytic profile correlated with oxygenscan parameters. We further confirm that oxygenscan parameters are associated with hydroxyurea treatment status. These results support the biological relevance of oxygenscan parameters and emphasize that longitudinal and advanced machine learning approaches are required to fully capture the SCD complexity.

Scientific Reports
Universitat Autònoma de Barcelona (ES), Hôpital Necker-Enfants Malades (FR), Hospital Sant Joan de Déu Barcelona (ES), University of Padua (IT), Radboud University Nijmegen (NL), Inserm (FR), Utrecht University (NL), Université Paris-Est Créteil (FR), Université Paris Cité (FR), Hospital de Sant Pau (ES), Erasmus MC (NL), Hospital Universitari Arnau de Vilanova (ES), Radboud University Medical Center (NL), University Medical Center Utrecht (NL), Sanquin (NL), Hospital for Sick Children Pediatric Center (US), Sorbonne Paris Cité (FR), Emma Kinderziekenhuis (NL), Assistance Publique – Hôpitaux de Paris (FR), Consorci Sanitari de Terrassa (ES), Maresme Health Consortium (ES), Vall d'Hebron Institut de Recerca (ES), Hospital General de Granollers (ES), Corporació Sanitària Parc Taulí (ES), Hospital Arnau de Vilanova (ES), Vall d'Hebron Hospital Universitari (ES), Department of Medical Sciences (BY), Établissement Français du Sang (FR), Mútua Terrassa (ES), Hospital de Mataró (ES), Erasmus MC - Sophia Children’s Hospital (NL), Erasmus MC Cancer Institute (NL), Amsterdam University Medical Centers (NL), Biologie intégrée du globule rouge et de l'Erythropoïèse (FR), National Institute of Mental Health (US), Institut Mondor de Recherche Biomédicale (FR), Universidad Politécnica de Madrid (ES), University of Amsterdam (NL), Universitat Politècnica de Catalunya (ES)
Amsterdam University Medical Centers, European Commission, Università degli Studi di Padova, Universitair Medisch Centrum Utrecht, Instituto de Salud Carlos III, Horizon 2020
Zero hunger
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Hemoglobinopathies and Related Disorders
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