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Review
. 2025 Sep 6:101338.
doi: 10.1016/j.blre.2025.101338. Online ahead of print.

Metabolomics in sickle cell disease: Current knowledge and gaps - A scoping review

Sigrid van der Veen  1 , Judith J M Jans  2 , Eduard J van Beers  3 , Bart J Biemond  4 , Pablo Bartolucci  5 , Maria Paola Boaro  6 , Anna Collado Gimbert  7 , Raffaella Colombatti  8 , Mirco D'Agnolo  9 , Karin J Fijnvandraat  10 , Amira Idrizovic  11 , Petros Kountouris  12 , Mar Mañú Pereira  13 , Elisabetta Mezzalira  14 , Minke A E Rab  15 , Anita W Rijneveld  16 , Tiziana Sanavia  17 , Nanda M Verhoeven-Duif  18 , Marjon H Cnossen  19
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Free article
Review

Metabolomics in sickle cell disease: Current knowledge and gaps - A scoping review

Sigrid van der Veen et al. Blood Rev. .
Free article

Abstract

Sickle cell disease (SCD) has large phenotypic variability. Systematic metabolomic profiling may provide insights into phenotypes and treatment responses. We conducted a scoping review on associations between blood metabolites, SCD-related complications, and therapies in studies analyzing ≥10 metabolites in red blood cells, whole blood, and plasma. Lipidomics-focused studies were excluded. Fifteen studies were included, focusing on metabolic profiling, clinical outcomes, or therapies (hydroxyurea, transfusion, and mitapivat). Metabolic profiling differentiated SCD from healthy controls and patients with HbSS and HbSC genotypes. Associations with hemolysis, vaso-occlusive events, nephropathy, TRV, and mortality were identified. Overall, metabolites were involved in arginine, tryptophan, glutamate metabolism, glycolysis, pentose phosphate pathway, and the Lands cycle. Some metabolites showed opposite correlations across complications or sample types. Despite growing interest, gaps remain in study designs, metabolite selection, genotype representation, and underexplored complications and therapies. Standardized, large-scale metabolomics studies are needed to advance personalized treatment in SCD.

Keywords: Hemoglobinopathy; Mass spectrometry; Metabolism; Metabolomics; Sickle cell anemia; Sickle cell disease.

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Conflict of interest statement

Declaration of competing interest Bart J. Biemond received research funding from Sanquin, BMS, Pfizer, and Novartis; received honoraria from Sanofi; reports advisory board participation with Celgene, CSL Behring, Pfizer, and Novo Nordisk. Marjon H. Cnossen received research funding from Takeda, Pfizer, Bayer, CSL Behring, Novo Nordisk, Novartis, Nordic Pharma; reports advisory or consulting role with Roche, Bayer, and Novartis. Eduard J. van Beers received research funding from Agios Pharmaceuticals, Inc., and Vertex; reports consulting role with Agios Pharmaceuticals, Inc. The remaining authors declare no competing financial interest.

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