Evidence map›Paper›PMID 39928952›Full record

ArticleBlood advances2025

Cellular and biochemical heterogeneity contributes to the phenotypic diversity of transfusion-dependent β-thalassemia.

Konstantina Theocharaki, Alkmini T Anastasiadi, Sophia Delicou, Vassilis L Tzounakas, Ioanna Barla, Stella Rouvela, Evgenia Kazolia, Georgia Tzafa, George Mpekoulis, Theodore Gousdovas and 16 more

Abstract read
In one paragraph

Article in Blood advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

26 authors.

Konstantina TheocharakiDepartment of Biology, School of Science, National and Kapodistrian University of Athens, Athens, Greece.
Alkmini T AnastasiadiDepartment of Biology, School of Science, National and Kapodistrian University of Athens, Athens, Greece.ORCID 0009-0007-3165-7493
Sophia DelicouThalassemia and Sickle Cell Unit, Expertise Center of Hemoglobinopathies and their Complications, Hippokration General Hospital of Athens, Athens, Greece.
Vassilis L TzounakasDepartment of Biology, School of Science, National and Kapodistrian University of Athens, Athens, Greece.ORCID 0009-0002-3697-001X
Ioanna BarlaDepartment of Chemistry, School of Science, National and Kapodistrian University of Athens, Athens, Greece.ORCID 0000-0003-1352-7816
Stella RouvelaDepartment of Biology, School of Science, National and Kapodistrian University of Athens, Athens, Greece.
Evgenia KazoliaDepartment of Biology, School of Science, National and Kapodistrian University of Athens, Athens, Greece.
Georgia TzafaDepartment of Biology, School of Science, National and Kapodistrian University of Athens, Athens, Greece.
George MpekoulisDepartment of Microbiology, Laboratory of Molecular Virology, Hellenic Pasteur Institute, Athens, Greece.ORCID 0000-0003-0043-7993
Theodore GousdovasHematology Laboratory-Blood Bank, Aretaieio Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Efthymia PavlouBlood Bank and Haemophilia Unit, Hippokration General Hospital of Athens, Athens, Greece.
Ioannis V KostopoulosDepartment of Biology, School of Science, National and Kapodistrian University of Athens, Athens, Greece.ORCID 0000-0003-1152-6959
Athanassios D VelentzasDepartment of Biology, School of Science, National and Kapodistrian University of Athens, Athens, Greece.ORCID 0000-0002-9755-395X
Nikolaos SimantirisDepartment of Informatics, Ionian University, Corfu, Greece.
Aikaterini XydakiThalassemia and Sickle Cell Unit, Expertise Center of Hemoglobinopathies and their Complications, Hippokration General Hospital of Athens, Athens, Greece.
Niki VassilakiDepartment of Microbiology, Laboratory of Molecular Virology, Hellenic Pasteur Institute, Athens, Greece.ORCID 0000-0001-7992-3438
Ersi VoskaridouCentre of Excellence in Rare Haematological (Haemoglobinopathies) & Rare Metabolic (Gaucher Disease) Diseases, Laiko General Hospital, Athens, Greece.
Ioanna-Katerina AggeliDepartment of Biology, School of Science, National and Kapodistrian University of Athens, Athens, Greece.
Efrosyni NomikouBlood Bank and Haemophilia Unit, Hippokration General Hospital of Athens, Athens, Greece.
Ourania TsitsilonisDepartment of Biology, School of Science, National and Kapodistrian University of Athens, Athens, Greece.
Efstathia PapageorgiouDepartment of Biomedical Sciences, School of Health & Caring Sciences, University of West Attica, Egaleo, Greece.
Nikolaos ThomaidisDepartment of Chemistry, School of Science, National and Kapodistrian University of Athens, Athens, Greece.ORCID 0000-0002-4624-4735
Evangelos GikasDepartment of Chemistry, School of Science, National and Kapodistrian University of Athens, Athens, Greece.
Marianna PolitouHematology Laboratory-Blood Bank, Aretaieio Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Veroniki KomninakaCentre of Excellence in Rare Haematological (Haemoglobinopathies) & Rare Metabolic (Gaucher Disease) Diseases, Laiko General Hospital, Athens, Greece.
Marianna H AntonelouDepartment of Biology, School of Science, National and Kapodistrian University of Athens, Athens, Greece.ORCID 0000-0003-3787-3596

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

abstractTransfusion-dependent thalassemia (TDT) is a type of protein aggregation disease. Its clinical heterogeneity imposes challenges in effective management. Red blood cell (RBC) variables may be clinically relevant as mechanistic parts or tellers of TDT pathophysiology. This is a cross-sectional study of RBC and plasma physiology in adult patients with TDT vs healthy control. TDT plasma was characterized by increased protein carbonylation, antioxidants, and larger than normal extracellular vesicles. RBCs were osmotically resistant but prone to oxidative hemolysis. They overexposed phosphatidylserine and exhibited pathologically low proteasome proteolytic activity (PPA), which correlated with metabolic markers of the disease. RBC ultrastructure was distorted, with splenectomy-related membrane pits of 300 to 800 nm. Plasma metabolomics revealed differences in heme metabolism, redox potential, short-chain fatty acids, and nitric oxide bioavailability, but also in catecholamine pathways. According to coefficient of variation assessment, hemolysis, iron homeostasis, PPA, and phosphatidylserine exposure were highly variable among patients, as opposed to RBC fragility and plasma antioxidants, amino acids, and catecholamines. Sex-based differences were detected in hemolysis, redox, and energy variables, whereas splenectomy-related differences referred to thrombotic risk, RBC morphology, and plasma metabolites with neuroendocrine activity. Hepcidin varied according to oxidative hemolysis and metabolic markers of bacterial activity. Patients with higher pretransfusion hemoglobin levels (>10 g/dL) presented mildly distorted profiles and lower membrane-associated PPA, whereas classification by severity of mutations revealed different levels of hemostasis, inflammation, plasma epinephrine, hexosamines, and methyltransferase activity markers. The currently reported heterogeneity of cellular and biochemical features probably contributes to the wide phenotypic diversity of TDT at clinical level.

Indexed as

Blood TransfusionErythrocytesThalassemiaAdultBiomarkersCross-Sectional StudiesFemaleHemolysisHumansMaleMetabolomicsMiddle AgedPhenotypeYoung AdultBiomarkers

Identifiers

PMID39928952
PMCPMC12051129

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.