{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T10:44:06Z","timestamp":1790419446815,"version":"4.1.0"},"reference-count":40,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2021,8,2]],"date-time":"2021-08-02T00:00:00Z","timestamp":1627862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Congenital anemias may be complicated by immune-mediated hemolytic crisis. Alloantibodies are usually seen in chronically transfused patients, and autoantibodies have also been described, although they are rarely associated with overt autoimmune hemolytic anemia (AIHA), a serious and potentially life-threatening complication. Given the lack of data on the AIHA diagnosis and management in congenital anemias, we retrospectively evaluated all clinically relevant AIHA cases occurring at a referral center for AIHA, hemoglobinopathies, and chronic hemolytic anemias, focusing on clinical management and outcome. In our cohort, AIHA had a prevalence of 1% (14\/1410 patients). The majority were warm AIHA. Possible triggers were recent transfusion, infection, pregnancy, and surgery. All the patients received steroid therapy as the first line, and about 25% required further treatment, including rituximab, azathioprine, intravenous immunoglobulins, and cyclophosphamide. Transfusion support was required in 57% of the patients with non-transfusion-dependent anemia, and recombinant human erythropoietin was safely administered in one third of the patients. AIHA in congenital anemias may be challenging both from a diagnostic and a therapeutic point of view. A proper evaluation of hemolytic markers, bone marrow compensation, and assessment of the direct antiglobulin test is mandatory.<\/jats:p>","DOI":"10.3390\/jcm10153439","type":"journal-article","created":{"date-parts":[[2021,8,3]],"date-time":"2021-08-03T08:16:39Z","timestamp":1627978599000},"page":"3439","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Autoimmune Hemolytic Anemia as a Complication of Congenital Anemias. A Case Series and Review of the Literature"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5701-599X","authenticated-orcid":false,"given":"Irene","family":"Motta","sequence":"first","affiliation":[{"name":"General Medicine Unit, Rare Diseases Center, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Department of Clinical Sciences and Community Health, Universit\u00e0 degli Studi di Milano, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9349-1627","authenticated-orcid":false,"given":"Juri","family":"Giannotta","sequence":"additional","affiliation":[{"name":"Hematology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Ferraresi","sequence":"additional","affiliation":[{"name":"General Medicine Unit, Rare Diseases Center, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kordelia","family":"Barbullushi","sequence":"additional","affiliation":[{"name":"Hematology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicoletta","family":"Revelli","sequence":"additional","affiliation":[{"name":"Laboratorio di Immunoematologia di Riferimento, Dipartimento di Medicina Trasfusionale ed Ematologia, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Graziadei","sequence":"additional","affiliation":[{"name":"General Medicine Unit, Rare Diseases Center, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilma","family":"Barcellini","sequence":"additional","affiliation":[{"name":"Hematology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0857-8379","authenticated-orcid":false,"given":"Bruno","family":"Fattizzo","sequence":"additional","affiliation":[{"name":"Hematology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Department of Oncology and Oncohematology, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1056\/NEJMra1510865","article-title":"Sickle Cell Disease","volume":"376","author":"Piel","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S0140-6736(17)31822-6","article-title":"Thalassaemia","volume":"391","author":"Taher","year":"2018","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1056\/NEJM199709113371107","article-title":"Pathogenesis and treatment of sickle cell disease","volume":"337","author":"Bunn","year":"1997","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1182\/asheducation-2018.1.377","article-title":"Inherited hemolytic anemia: A possessive beginner\u2019s guide","volume":"2018","author":"Mohandas","year":"2018","journal-title":"Hematol. Am. Soc. Hematol. Educ. Program"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3939","DOI":"10.1182\/blood-2008-07-161166","article-title":"Red cell membrane: Past, present, and future","volume":"112","author":"Mohandas","year":"2008","journal-title":"Blood"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1111\/bjh.15758","article-title":"How we manage patients with pyruvate kinase deficiency","volume":"184","author":"Grace","year":"2019","journal-title":"Br. J. Haematol."},{"key":"ref_7","unstructured":"Cappellini, M.D., Cohen, A., Porter, J., Taher, A., and Viprakasit, V. (2014). Guidelines for the Management of Transfusion Dependent Thalassaemia (TDT), Thalassemia International Federation. [3rd ed.]."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1182\/bloodadvances.2019001143","article-title":"American Society of Hematology 2020 guidelines for sickle cell disease: Transfusion support","volume":"4","author":"Chou","year":"2020","journal-title":"Blood Adv."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1111\/bjh.17484","article-title":"Acute human parvovirus B19 infection triggers immune-mediated transient bone marrow failure syndrome, extreme direct hyperbilirubinaemia and acute hepatitis in patients with hereditary haemolytic anaemias: Multicentre prospective pathophysiological study","volume":"193","author":"Elbadry","year":"2021","journal-title":"Br. J. Haematol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Barcellini, W., Zaninoni, A., Giannotta, J.A., and Fattizzo, B. (2020). New Insights in Autoimmune Hemolytic Anemia: From Pathogenesis to Therapy Stage 1. J. Clin. Med., 9.","DOI":"10.3390\/jcm9123859"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2930","DOI":"10.1111\/trf.13257","article-title":"Detection of red blood cell antibodies in mitogen-stimulated cultures from patients with hereditary spherocytosis","volume":"55","author":"Zaninoni","year":"2015","journal-title":"Transfusion"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1080\/17474086.2020.1754791","article-title":"Autoimmune hemolytic anemia in adults: Primary risk factors and diagnostic procedures","volume":"13","author":"Barcellini","year":"2020","journal-title":"Expert Rev. Hematol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"100648","DOI":"10.1016\/j.blre.2019.100648","article-title":"Diagnosis and treatment of autoimmune hemolytic anemia in adults: Recommendations from the First International Consensus Meeting","volume":"41","author":"Jager","year":"2020","journal-title":"Blood Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"E169","DOI":"10.1002\/ajh.23800","article-title":"Retrospective cohort study of 205 cases with congenital dyserythropoietic anemia type II: Definition of clinical and molecular spectrum and identification of new diagnostic scores","volume":"89","author":"Russo","year":"2014","journal-title":"Am. J. Hematol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2930","DOI":"10.1182\/blood-2014-06-583021","article-title":"Clinical heterogeneity and predictors of outcome in primary autoimmune hemolytic anemia: A GIMEMA study of 308 patients","volume":"124","author":"Barcellini","year":"2014","journal-title":"Blood"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"635670","DOI":"10.1155\/2015\/635670","article-title":"Clinical Applications of Hemolytic Markers in the Differential Diagnosis and Management of Hemolytic Anemia","volume":"2015","author":"Barcellini","year":"2015","journal-title":"Dis. Markers"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"102342","DOI":"10.1016\/j.bcmd.2019.102342","article-title":"Predictors of autoimmune hemolytic anemia in beta-thalassemia patients with underlying red blood cells autoantibodies","volume":"79","author":"Khaled","year":"2019","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_18","first-page":"452","article-title":"In vitro quantification of anti-red blood cell antibody production in idiopathic autoimmune haemolytic anaemia: Effect of mitogen and cytokine stimulation","volume":"111","author":"Barcellini","year":"2000","journal-title":"Br. J. Haematol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"610931","DOI":"10.1155\/2015\/610931","article-title":"Frequency of Red Cell Alloimmunization and Autoimmunization in Thalassemia Patients: A Report from Eastern India","volume":"2015","author":"Datta","year":"2015","journal-title":"Adv. Hematol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1111\/trf.12348","article-title":"Transfusion complications in thalassemia patients: A report from the Centers for Disease Control and Prevention (CME)","volume":"54","author":"Vichinsky","year":"2014","journal-title":"Transfusion"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"161","DOI":"10.4103\/0973-6247.164268","article-title":"Direct antiglobulin test positivity in multi-transfused thalassemics","volume":"10","author":"Jain","year":"2016","journal-title":"Asian J. Transfus. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"84","DOI":"10.4103\/0973-6247.137438","article-title":"Alloimmunization and autoimmunization in transfusion dependent thalassemia major patients: Study on 319 patients","volume":"8","author":"Dhawan","year":"2014","journal-title":"Asian J. Transfus. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s12288-013-0311-y","article-title":"Red blood cell antibodies in thalassemia patients in northern India: Risk factors and literature review","volume":"30","author":"Elhence","year":"2014","journal-title":"Indian J. Hematol. Blood Transfus."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"21079","DOI":"10.1038\/s41598-020-78333-y","article-title":"A study of red blood cell alloimmunization and autoimmunization among 200 multitransfused Egyptian beta thalassemia patients","volume":"10","author":"Salama","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1111\/ijlh.12362","article-title":"Frequency and specificity of red cell antibodies in thalassemia patients in Albania","volume":"37","author":"Seferi","year":"2015","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"88","DOI":"10.4103\/0973-6247.172179","article-title":"Study of alloimmunization and autoimmunization in Iranian beta-thalassemia major patients","volume":"10","author":"Davari","year":"2016","journal-title":"Asian J. Transfus. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1056\/NEJM199006073222301","article-title":"Alloimmunization in sickle cell anemia and transfusion of racially unmatched blood","volume":"322","author":"Vichinsky","year":"1990","journal-title":"N. Engl. J. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1046\/j.1537-2995.2002.00007.x","article-title":"Clinical significance of RBC alloantibodies and autoantibodies in sickle cell patients who received transfusions","volume":"42","author":"Aygun","year":"2002","journal-title":"Transfusion"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1046\/j.1365-2141.1999.01127.x","article-title":"Erythrocyte autoantibodies in paediatric patients with sickle cell disease receiving transfusion therapy: Frequency, characteristics and significance","volume":"104","author":"Castellino","year":"1999","journal-title":"Br. J. Haematol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1046\/j.1537-2995.1987.27187121485.x","article-title":"Experience with donors matched for minor blood group antigens in patients with sickle cell anemia who are receiving chronic transfusion therapy","volume":"27","author":"Ambruso","year":"1987","journal-title":"Transfusion"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1159\/000205170","article-title":"High-dose intravenous immunoglobulin in the management of autoimmune hemolytic anemia complicating thalassemia major","volume":"83","author":"Argiolu","year":"1990","journal-title":"Acta Haematol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1159\/000207366","article-title":"beta 0-Thalassemia complicated by autoimmune hemolytic anemia. Globin synthesis during immunosuppressive therapy","volume":"63","author":"Cividalli","year":"1980","journal-title":"Acta Haematol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"128","DOI":"10.4103\/0973-6247.137454","article-title":"Resolution of alloimmunization and refractory autoimmune hemolytic anemia in a multi-transfused beta-thalassemia major patient","volume":"8","author":"Philip","year":"2014","journal-title":"Asian J. Transfus. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1097\/00043426-200606000-00017","article-title":"Transfusion-related immune hemolytic anemia in thalassemic patients: Report of 2 cases","volume":"28","author":"Koussi","year":"2006","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1001\/archinte.1981.00340080127029","article-title":"Combined sickle cell disease and autoimmune hemolytic anemia","volume":"141","author":"Chaplin","year":"1981","journal-title":"Arch. Intern. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1002\/jca.2920060413","article-title":"Problems of chronic transfusion in sickle cell disease","volume":"6","author":"Orlina","year":"1991","journal-title":"J. Clin. Apher."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"622","DOI":"10.3324\/haematol.2020.250522","article-title":"Efficacy of recombinant erythropoietin in autoimmune hemolytic anemia: A multicenter international study","volume":"106","author":"Fattizzo","year":"2021","journal-title":"Haematologica"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1002\/ajh.25742","article-title":"Complement activation in sickle cell disease: Dependence on cell density, hemolysis and modulation by hydroxyurea therapy","volume":"95","author":"Roumenina","year":"2020","journal-title":"Am. J. Hematol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.1111\/trf.16143","article-title":"Role of therapeutic plasma exchanges in refractory severe warm autoimmune hemolytic anemia: Presentation of two case reports","volume":"60","author":"Cid","year":"2020","journal-title":"Transfusion"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.molmed.2016.01.004","article-title":"Heme: Modulator of Plasma Systems in Hemolytic Diseases","volume":"22","author":"Roumenina","year":"2016","journal-title":"Trends Mol. Med."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/15\/3439\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:39:12Z","timestamp":1760164752000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/15\/3439"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,2]]},"references-count":40,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["jcm10153439"],"URL":"https:\/\/doi.org\/10.3390\/jcm10153439","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,2]]}}}