{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:57:14Z","timestamp":1790848634874,"version":"4.1.0"},"reference-count":103,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Transfusion Medicine"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Sickle cell disease (SCD) is one of the most common inherited haemoglobin disorders worldwide and is associated with substantial morbidity, premature mortality and lifelong healthcare utilisation. Red blood cell (RBC) transfusion remains a cornerstone of SCD management and is indispensable for the treatment and prevention of life\u2010threatening complications, including acute chest syndrome, ischaemic stroke, severe anaemia and perioperative complications. Despite its undeniable therapeutic benefits, repeated transfusions are accompanied by important adverse consequences, including alloimmunisation, iron overload, delayed haemolytic transfusion reactions and transfusion\u2010transmitted infections. Beyond haemoglobin S dilution, transfusion therapy interacts with the chronic inflammatory and immune\u2010activated milieu characteristic of SCD. Persistent haemolysis, endothelial dysfunction, nitric oxide depletion, leukocyte and platelet activation collectively influence both disease severity and transfusion\u2010related immune responses, thereby contributing to alloantibody formation and other immunological complications. This review provides a comprehensive overview of the clinical indications, transfusion strategies, immunological mechanisms and transfusion\u2010related complications in patients with SCD. Particular emphasis is placed on the cellular and molecular mechanisms underlying alloimmunisation, including the roles of antigen\u2010presenting cells, CD4\n                    <jats:sup>+<\/jats:sup>\n                    T lymphocytes, B cells and regulatory T cells. Contemporary approaches to minimising transfusion\u2010related complications\u2014including extended antigen matching, molecular RBC genotyping, routine alloantibody screening, iron chelation therapy and emerging immunomodulatory strategies\u2014are critically discussed. In addition, the review highlights regional challenges and evolving transfusion practices in Saudi Arabia, including newborn screening programmes, comprehensive care initiatives, donor\u2013recipient antigen mismatch and implementation of national transfusion strategies. By integrating current evidence from clinical medicine, immunology and transfusion science, this review provides clinicians with an updated framework for optimising transfusion therapy while minimising preventable complications and improving long\u2010term outcomes in patients with SCD.\n                  <\/jats:p>","DOI":"10.1111\/tme.70122","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:18:08Z","timestamp":1790846288000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Red blood cell transfusion in sickle cell disease: From clinical necessity to immunological complexity"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0546-6697","authenticated-orcid":false,"given":"Mohamed Eltaib","family":"Elmobark","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy Jazan University  Jazan Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0777-8256","authenticated-orcid":false,"given":"Mohamd Z.","family":"Sayed\u2010Ahmed","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, College of Pharmacy Jazan University  Jazan Saudi Arabia"},{"name":"Pharmacy Practice Research Unit, Department of Pharmacy Practice, College of Pharmacy Jazan University  Jazan Saudi Arabia"},{"name":"Department of Internal Medicine and Infectious Diseases, Faculty of Veterinary Medicine Mansoura University  Mansoura Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0786-4779","authenticated-orcid":false,"given":"Mohammed","family":"Al\u2010Rasheed","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, College of Veterinary Medicine King Faisal University  Al\u2010Hofuf Al\u2010Ahsa Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7961-1247","authenticated-orcid":false,"given":"Mohamed","family":"Marzok","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, College of Veterinary Medicine King Faisal University  Al\u2010Hofuf Al\u2010Ahsa Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4860-0166","authenticated-orcid":false,"given":"Sivakumar S.","family":"Moni","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy Jazan University  Jazan Saudi Arabia"},{"name":"Health Research Centre Jazan University  Jazan Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1839-8534","authenticated-orcid":false,"given":"Mahmoud","family":"Elalfy","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, College of Veterinary Medicine King Faisal University  Al\u2010Hofuf Al\u2010Ahsa Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6145-4466","authenticated-orcid":false,"given":"Siddig Ibrahim","family":"Abdelwahab","sequence":"additional","affiliation":[{"name":"Health Research Centre Jazan University  Jazan Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5250-6172","authenticated-orcid":false,"given":"Mohamed Abdo","family":"Rizk","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, College of Veterinary Medicine King Faisal University  Al\u2010Hofuf Al\u2010Ahsa Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"crossref","first-page":"341","DOI":"10.3390\/hemato3020024","article-title":"Sickle cell disease, a 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