{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T20:41:14Z","timestamp":1789072874624,"version":"build-2803163510"},"reference-count":48,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T00:00:00Z","timestamp":1739232000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the State Assignment of the Ministry of Science and Higher Education of the Russian Federation","award":["075-00263-25-00"],"award-info":[{"award-number":["075-00263-25-00"]}]},{"name":"the State Assignment of the Ministry of Science and Higher Education of the Russian Federation","award":["23-15-00142"],"award-info":[{"award-number":["23-15-00142"]}]},{"name":"the Russian Scientific Foundation","award":["075-00263-25-00"],"award-info":[{"award-number":["075-00263-25-00"]}]},{"name":"the Russian Scientific Foundation","award":["23-15-00142"],"award-info":[{"award-number":["23-15-00142"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Hemolysis during severe diseases (malaria, hemorrhagic stroke, sickle cell disease, etc.) and blood transfusion induces the release of free hemoglobin, which degrades to highly reactive and toxic compounds\u2014hemin and hematin. Oxidized heme derivatives induce platelet activation, aggregation, and degranulation, leading to prothrombotic and inflammatory events. In the present study, we showed that hematin is a more potent agonist of platelet activation than hemin, and using several methods, including the original laser diffraction method, flow cytometry, and confocal microscopy, we demonstrated that hematin at low doses induces platelet activation and aggregation without reducing cell viability and affecting calcium efflux. On the contrary, hematin at high concentrations triggered phosphatidylserine exposure, severe loss of platelet viability, and calcium dysregulation, which was not inhibited by cGMP\/PKG and cAMP\/PKA pathways. Additionally, we showed that albumin could initiate disaggregation processes in hematin-activated platelets.<\/jats:p>","DOI":"10.3390\/cells14040255","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T09:36:05Z","timestamp":1739266565000},"page":"255","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Analysis of Ferric Protoporphyrin IX Effects on Human Platelets: Hematin Is a More Potent Agonist than Hemin"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3061-4420","authenticated-orcid":false,"given":"Diana M.","family":"Mikhailova","sequence":"first","affiliation":[{"name":"Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 44 Thorez Ave., 194223 Saint Petersburg, Russia"},{"name":"Department of Cytology and Histology, Saint Petersburg State University, 7\/9 Universitetskaya Emb., 199034 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5322-7044","authenticated-orcid":false,"given":"Julia","family":"Sudnitsyna","sequence":"additional","affiliation":[{"name":"Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 44 Thorez Ave., 194223 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Polina","family":"Kovgan","sequence":"additional","affiliation":[{"name":"Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 44 Thorez Ave., 194223 Saint Petersburg, Russia"},{"name":"Institute of Biomedical Systems and Biotechnologies, Peter the Great Saint Petersburg Polytechnic University, 195251 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidia","family":"Naida","sequence":"additional","affiliation":[{"name":"Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 44 Thorez Ave., 194223 Saint Petersburg, Russia"},{"name":"Institute of Biomedical Systems and Biotechnologies, Peter the Great Saint Petersburg Polytechnic University, 195251 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Kharazova","sequence":"additional","affiliation":[{"name":"Department of Cytology and Histology, Saint Petersburg State University, 7\/9 Universitetskaya Emb., 199034 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5978-2105","authenticated-orcid":false,"given":"Igor","family":"Mindukshev","sequence":"additional","affiliation":[{"name":"Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 44 Thorez Ave., 194223 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1470-0791","authenticated-orcid":false,"given":"Stepan","family":"Gambaryan","sequence":"additional","affiliation":[{"name":"Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 44 Thorez Ave., 194223 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1182\/blood-2013-04-495887","article-title":"Heme triggers TLR4 signaling leading to endothelial cell activation and vaso-occlusion in murine sickle cell disease","volume":"123","author":"Belcher","year":"2014","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1182\/blood-2013-03-489245","article-title":"Complement activation by heme as a secondary hit for atypical hemolytic uremic syndrome","volume":"122","author":"Frimat","year":"2013","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1038\/ni.3590","article-title":"Heme drives hemolysis-induced susceptibility to infection via disruption of phagocyte functions","volume":"17","author":"Martins","year":"2016","journal-title":"Nat. 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