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In the present retrospective study, we compared serum samples from transfusion\u2010dependent patients with \u03b2\u2010thalassaemia major and intermedia, hereditary spherocytosis and sickle cell disease (SCD). Haemolysis, transfusions and ineffective erythropoiesis contribute to haem and iron overload in haemolytic patients. In all cohorts we observed increased systemic haem and iron levels associated with scavenger depletion and toxic \u2018free\u2019 species formation. Endothelial dysfunction, oxidative stress and inflammation markers were significantly increased compared to healthy donors. In multivariable logistic regression analysis, oxidative stress markers remained significantly associated with both haem\u2010 and iron\u2010related parameters, while soluble vascular cell adhesion molecule 1 (sVCAM\u20101), soluble endothelial selectin (sE\u2010selectin) and tumour necrosis factor \u03b1 (TNF\u03b1) showed the strongest association with haem\u2010related parameters and soluble intercellular adhesion molecule 1 (sICAM\u20101), sVCAM\u20101, interleukin 6 (IL\u20106) and vascular endothelial growth factor (VEGF) with iron\u2010related parameters. While hereditary spherocytosis was associated with the highest IL\u20106 and TNF\u03b1 levels, \u03b2\u2010thalassaemia major showed limited inflammation compared to SCD. The sVCAM1 increase was significantly lower in patients with SCD receiving exchange compared to simple transfusions. The present results support the involvement of free haem\/iron species in the pathogenesis of vascular dysfunction and sterile inflammation in haemolytic diseases, irrespective of the underlying haemolytic mechanism, and highlight the potential therapeutic benefit of iron\/haem scavenging therapies in these conditions.<\/jats:p>","DOI":"10.1111\/bjh.17361","type":"journal-article","created":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T05:44:39Z","timestamp":1615873479000},"page":"637-658","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Vasculo\u2010toxic and pro\u2010inflammatory action of unbound haemoglobin, haem and iron in transfusion\u2010dependent patients with haemolytic anaemias"],"prefix":"10.1111","volume":"193","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1631-8286","authenticated-orcid":false,"given":"Francesca","family":"Vinchi","sequence":"first","affiliation":[{"name":"Iron Research Program New York Blood Center New York NY USA"},{"name":"Department of Pathology and Laboratory Medicine Weill Cornell Medicine Cornell University New York NY USA"},{"name":"Molecular Medicine Partnership Unit (MMPU) European Molecular Biology Laboratory (EMBL) Heidelberg University Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Sparla","sequence":"additional","affiliation":[{"name":"Center for Translational Biomedical Iron Research Department of Pediatric Oncology Hematology, Immunology and Pulmonology University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara T.","family":"Passos","sequence":"additional","affiliation":[{"name":"Iron Research Program New York Blood Center New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richa","family":"Sharma","sequence":"additional","affiliation":[{"name":"Iron Research Program New York Blood Center New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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