{"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":1791822501299,"version":"4.3.4"},"reference-count":129,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T00:00:00Z","timestamp":1712880000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Autoimmune hemolytic anemias (AIHAs) are conditions involving the production of antibodies against one\u2019s own red blood cells (RBCs). These can be primary with unknown cause or secondary (by association with diseases or infections). There are several different categories of AIHAs recognized according to their features in the direct antiglobulin test (DAT). (1) Warm-antibody AIHA (wAIHA) exhibits a pan-reactive IgG autoantibody recognizing a portion of band 3 (wherein the DAT may be positive with IgG, C3d or both). Treatment involves glucocorticoids and steroid-sparing agents and may consider IVIG or monoclonal antibodies to CD20, CD38 or C1q. (2) Cold-antibody AIHA due to IgMs range from cold agglutinin syndrome (CAS) to cold agglutin disease (CAD). These are typically specific to the Ii blood group system, with the former (CAS) being polyclonal and the latter (CAD) being a more severe and monoclonal entity. The DAT in either case is positive only with C3d. Foundationally, the patient is kept warm, though treatment for significant complement-related outcomes may, therefore, capitalize on monoclonal options against C1q or C5. (3) Mixed AIHA, also called combined cold and warm AIHA, has a DAT positive for both IgG and C3d, with treatment approaches inclusive of those appropriate for wAIHA and cold AIHA. (4) Paroxysmal cold hemoglobinuria (PCH), also termed Donath\u2013Landsteiner test-positive AIHA, has a DAT positive only for C3d, driven upstream by a biphasic cold-reactive IgG antibody recruiting complement. Although usually self-remitting, management may consider monoclonal antibodies to C1q or C5. (5) Direct antiglobulin test-negative AIHA (DAT-neg AIHA), due to IgG antibody below detection thresholds in the DAT, or by non-detected IgM or IgA antibodies, is managed as wAIHA. (6) Drug-induced immune hemolytic anemia (DIIHA) appears as wAIHA with DAT IgG and\/or C3d. Some cases may resolve after ceasing the instigating drug. (7) Passenger lymphocyte syndrome, found after transplantation, is caused by B-cells transferred from an antigen-negative donor whose antibodies react with a recipient who produces antigen-positive RBCs. This comprehensive review will discuss in detail each of these AIHAs and provide information on diagnosis, pathophysiology and treatment modalities.<\/jats:p>","DOI":"10.3390\/ijms25084296","type":"journal-article","created":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T11:09:20Z","timestamp":1712920160000},"page":"4296","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Autoimmune Hemolytic Anemias: Classifications, Pathophysiology, Diagnoses and Management"],"prefix":"10.3390","volume":"25","author":[{"given":"Melika","family":"Loriamini","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5B 1W8, Canada"},{"name":"Centre for Innovation, Canadian Blood Services, Keenan Research Centre, Room 420, 30 Bond Street, Toronto, ON M5B 1W8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5297-6406","authenticated-orcid":false,"given":"Christine","family":"Cserti-Gazdewich","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5B 1W8, Canada"},{"name":"Laboratory Medicine Program, Blood Transfusion Laboratory, University Health Network, Toronto, ON M5G 2C4, Canada"},{"name":"Blood Disorders Program, Department of Medical Oncology and Hematology, University Health Network, Toronto, ON M5G 2C4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8974-2451","authenticated-orcid":false,"given":"Donald R.","family":"Branch","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5B 1W8, Canada"},{"name":"Centre for Innovation, Canadian Blood Services, Keenan Research Centre, Room 420, 30 Bond Street, Toronto, ON M5B 1W8, Canada"},{"name":"Department of Medicine, University of Toronto, Toronto, ON M5B 1W8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1136\/bmj.2.5706.381","article-title":"Autoimmune haemolytic anaemias","volume":"2","author":"Dacie","year":"1970","journal-title":"Br. 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