{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:28:21Z","timestamp":1791822501701,"version":"4.3.4"},"reference-count":54,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T00:00:00Z","timestamp":1747699200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["1K23HL15182"],"award-info":[{"award-number":["1K23HL15182"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Mixed autoimmune hemolytic anemia (AIHA) is a rare and clinically complex hematologic disorder defined by the simultaneous presence of both warm and cold autoantibodies, resulting in severe and often treatment\u2010resistant hemolysis. Due to variability in diagnostic criteria and limited data, a comprehensive understanding of its epidemiology, clinical characteristics, and management remains incomplete. To address these gaps, we performed a systematic literature review employing stringent diagnostic criteria to evaluate epidemiologic patterns, clinical features, and therapeutic outcomes. Our analysis included 81 patients identified across 35 studies, revealing a median age of 45\u2009years and a notable female predominance (2.25:1). Autoimmune diseases constituted the most frequent underlying etiology, followed by hematologic malignancies and infections. Patients exhibited significant anemia, with median nadir hemoglobin levels reaching 5.6\u2009g\/dL. Corticosteroids represented the most common therapeutic intervention; however, only 43% of patients achieved remission, while 37% experienced chronic hemolysis, and mortality reached 11%. Many patients required multiple lines of therapy, including rituximab and cytotoxic agents, highlighting the disease's refractory nature and management complexity. The substantial variability in diagnostic and therapeutic approaches emphasizes an urgent need for standardized diagnostic criteria, earlier integration of combination therapies, and exploration of innovative treatment modalities. Future prospective, multicenter studies are essential to refine disease recognition, optimize therapeutic strategies, and ultimately improve patient outcomes in mixed AIHA.<\/jats:p>","DOI":"10.1002\/ajh.27721","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T09:18:39Z","timestamp":1747732719000},"page":"1397-1407","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Mixed Autoimmune Hemolytic Anemia: A Systematic Review of Epidemiology, Clinical Characteristics, Therapies, and Outcomes"],"prefix":"10.1002","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5719-9685","authenticated-orcid":false,"given":"Jeremy W.","family":"Jacobs","sequence":"first","affiliation":[{"name":"Department of Pathology, Microbiology &amp; Immunology Vanderbilt University  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheharyar","family":"Raza","sequence":"additional","affiliation":[{"name":"Laboratory Medicine and Pathobiology University of Toronto  Toronto Ontario Canada"},{"name":"Canadian Blood Services Medical Affairs and Innovation  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Landon M.","family":"Clark","sequence":"additional","affiliation":[{"name":"Vanderbilt University School of Medicine  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura D.","family":"Stephens","sequence":"additional","affiliation":[{"name":"Department of Pathology University of California San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth S.","family":"Allen","sequence":"additional","affiliation":[{"name":"Department of Pathology University of California San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer S.","family":"Woo","sequence":"additional","affiliation":[{"name":"Department of Pathology City of Hope Comprehensive Cancer Center  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5998-2083","authenticated-orcid":false,"given":"Rachel Lane","family":"Walden","sequence":"additional","affiliation":[{"name":"Annette and Irwin Eskind Family Biomedical Library and Learning Center, Vanderbilt University  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina A.","family":"Figueroa Villalba","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Yale School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1785-2245","authenticated-orcid":false,"given":"Christopher A.","family":"Tormey","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Yale School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4274-2354","authenticated-orcid":false,"given":"Caroline G.","family":"Stanek","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9480-2762","authenticated-orcid":false,"given":"Brian D.","family":"Adkins","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Texas Southwestern Medical Center  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8181-9517","authenticated-orcid":false,"given":"Evan M.","family":"Bloch","sequence":"additional","affiliation":[{"name":"Division of Transfusion Medicine, Department of Pathology Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8422-9480","authenticated-orcid":false,"given":"Garrett S.","family":"Booth","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology &amp; 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