{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T08:06:56Z","timestamp":1789632416595,"version":"build-2803163510"},"reference-count":101,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T00:00:00Z","timestamp":1764720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Background: Biological sex differences are well-recognized as non-negligible factors in implementing precision medicine practice. Sex chromosomes influence protein expression and signaling, and thus cellular pathways are often regulated differently. Additionally, the importance of sex as a biological variable has gained significant traction in biomedical research, including transfusion medicine. Regarding transfusion medicine, several studies reveal the role of gender in blood transfusion, blood donors\u2019 behavior towards donation, blood products\u2019 composition and storage, transfusion therapy, and possibly post-transfusion patient outcomes. Methods: In this review, the role of sex and gender in the whole transfusion chain (from the blood donor to the blood product and the patient) is assessed and summarized using data from observational studies, registry analyses, and randomized trials. Results: Female donors face higher deferral rates due to biological factors (iron deficiency, low hemoglobin, pregnancy) and sociocultural factors (caregiving responsibilities, misinformation). However, women are more likely to donate based on empathy, moral duty, or community responsibility and are more consistent in sustaining voluntary donation during crises. Men donate more frequently, typically driven by external motivators, and provide red blood cell (RBC) products with higher hemoglobin content, whereas RBCs from female donors exhibit greater metabolic stability and reduced hemolysis during storage. Plasma from multiparous women possibly contains alloantibodies associated with adverse transfusion reactions, namely transfusion-related acute lung injury (TRALI). Platelet function also varies by sex, though its possible clinical impact is still unknown. Although observational studies suggest sex-mismatched transfusions are associated with increased morbidity and mortality\u2014particularly in transfusions from female donors to male recipients\u2014large registries and randomized controlled trials show inconsistent or negligible effect on survival. Conclusions: Donor and recipient sex are emerging variables of possible clinical importance in transfusion practice. Incorporating sex-informed insights into donor recruitment, blood product handling and transfusion policies may improve safety while advancing precision medicine. Further large-scale trials are needed to elucidate the impact of sex in transfusion, identify and eliminate possible risks, and bridge the gap between biological insights and clinical practice.<\/jats:p>","DOI":"10.3390\/jpm15120592","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T16:37:02Z","timestamp":1764952622000},"page":"592","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["When Blood Remembers Its Sex: Toward Truly Personalized Transfusion Medicine"],"prefix":"10.3390","volume":"15","author":[{"given":"Sotirios P.","family":"Fortis","sequence":"first","affiliation":[{"name":"Laboratory of Reliability and Quality Control in Laboratory Hematology (HemQcR), Department of Bio-Medical Sciences, School of Health & Caring Sciences, University of West Attica (UniWA), 12243 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1635-7309","authenticated-orcid":false,"given":"Styliani","family":"Kokoris","sequence":"additional","affiliation":[{"name":"Laboratory of Hematology and Blood Bank Unit, \u201cAttikon\u201d University General Hospital, School of Medicine, National and Kapodistrian University of Athens, 11521 Athens, Greece"},{"name":"Postgraduate Program \u201cThrombosis, Bleeding, and Transfusion Medicine\u201d, School of Medicine, National and Kapodistrian University of Athens, 11521 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavlos","family":"Kelepousidis","sequence":"additional","affiliation":[{"name":"Postgraduate Program \u201cThrombosis, Bleeding, and Transfusion Medicine\u201d, School of Medicine, National and Kapodistrian University of Athens, 11521 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Dryllis","sequence":"additional","affiliation":[{"name":"Laboratory of Reliability and Quality Control in Laboratory Hematology (HemQcR), Department of Bio-Medical Sciences, School of Health & Caring Sciences, University of West Attica (UniWA), 12243 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria-Aspasia","family":"Kosma","sequence":"additional","affiliation":[{"name":"Laboratory of Reliability and Quality Control in Laboratory Hematology (HemQcR), Department of Bio-Medical Sciences, School of Health & Caring Sciences, University of West Attica (UniWA), 12243 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodoros","family":"Pittaras","sequence":"additional","affiliation":[{"name":"Hematology Laboratory and \u0392lood Bank, Aretaieion Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3915-1829","authenticated-orcid":false,"given":"Anastasios G.","family":"Kriebardis","sequence":"additional","affiliation":[{"name":"Laboratory of Reliability and Quality Control in Laboratory Hematology (HemQcR), Department of Bio-Medical Sciences, School of Health & Caring Sciences, University of West Attica (UniWA), 12243 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Valsami","sequence":"additional","affiliation":[{"name":"Postgraduate Program \u201cThrombosis, Bleeding, and Transfusion Medicine\u201d, School of Medicine, National and Kapodistrian University of Athens, 11521 Athens, Greece"},{"name":"Hematology Laboratory and \u0392lood Bank, Aretaieion Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/nrclinonc.2010.227","article-title":"Predictive, personalized, preventive, participatory (P4) cancer medicine","volume":"8","author":"Hood","year":"2011","journal-title":"Nat. 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