{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:23:32Z","timestamp":1786116212234,"version":"build-2736575974"},"reference-count":116,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibodies"],"abstract":"<jats:p>Sickle cell disease (SCD) represents one of the most complex hematological diseases leading to a lifetime of physiological crises characterized by chronic hemolysis, inflammation, hypoxia, and anemia with changes to body systems that result in patients having shorter lifespans. Transfusions, either simple or as part of red cell exchanges, are often needed to lower the hemoglobin S levels to minimize the possibility of sickling of red blood cells (RBCs) and provide patients with greater oxygen carrying capacity. However, hemolysis in SCD patients is a common finding\/presentation of the disease, especially during acute crises. One of the ensuing complications of a life of transfusions is the development of alloantibodies to RBC antigens despite partial or extended matching. This is further complicated by formation of autoantibodies even in the setting of RBC matching, suggesting that a hyperactive immune response in these patients is primed to respond with formation of antibodies. In a sub-cohort of patients, no antibodies are detected despite extensive investigation, and the ensuing hemolysis requires minimizing exposure to RBC transfusions to avoid developing a greater hemolytic process. Instead, immunosuppression or monoclonals that target complement or cytokines shown to be involved in this type of hemolysis are necessary. In this context, this narrative review will present antibody-dependent and antibody-independent mechanisms of hemolysis in SCD, including therapeutic approaches that target specific areas of the immune response that are possibly involved in the destruction of RBCs.<\/jats:p>","DOI":"10.3390\/antib15040070","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T08:08:02Z","timestamp":1786003682000},"page":"70","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Antibody-Dependent and Antibody-Independent Hemolysis in Sickle Cell Disease"],"prefix":"10.3390","volume":"15","author":[{"given":"Raeshun T.","family":"Glover","sequence":"first","affiliation":[{"name":"Department of Pathology, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5424-5519","authenticated-orcid":false,"given":"Robert W.","family":"Maitta","sequence":"additional","affiliation":[{"name":"Department of Pathology, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1177\/0033354919881438","article-title":"Reducing Health Care Disparities in Sickle Cell Disease: A Review","volume":"134","author":"Lee","year":"2019","journal-title":"Public Health Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1001\/jama.2022.10233","article-title":"Sickle Cell Disease: A Review","volume":"328","author":"Kavanagh","year":"2022","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"248","DOI":"10.15585\/mmwr.mm7312a1","article-title":"Birth Prevalence of Sickle Cell Disease and County-Level Social Vulnerability\u2014Sickle Cell Data Collection Program, 11 States, 2016\u20132020","volume":"73","author":"Kayle","year":"2024","journal-title":"MMWR Morb. 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