{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:05:10Z","timestamp":1789657510813,"version":"4.0.1"},"reference-count":44,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T00:00:00Z","timestamp":1747008000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T00:00:00Z","timestamp":1747008000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012023","name":"Stichting Sanquin Bloedvoorziening","doi-asserted-by":"publisher","award":["PPO\u2010SHS\u2010 2022\u201022.13\/L2687"],"award-info":[{"award-number":["PPO\u2010SHS\u2010 2022\u201022.13\/L2687"]}],"id":[{"id":"10.13039\/501100012023","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012023","name":"Stichting Sanquin Bloedvoorziening","doi-asserted-by":"publisher","award":["PPOC\u201019\u201025\/L2476"],"award-info":[{"award-number":["PPOC\u201019\u201025\/L2476"]}],"id":[{"id":"10.13039\/501100012023","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Transfusion"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Autoimmune hemolytic anemia (AIHA) is typically mediated by immunoglobulin G (IgG) or immunoglobulin M (IgM) antibodies, and more rarely by immunoglobulin A (IgA). The mechanism of red blood cell (RBC) destruction in IgA\u2010mediated AIHA is not well understood. We report a case of severe AIHA with intravascular hemolysis, positive for IgA. Hemolysis did not subside despite multiple transfusions and treatment lines, leading to a fatal outcome. Here, we set out to investigate underlying pathophysiological mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Design and Methods<\/jats:title>\n                    <jats:p>To investigate the underlying pathophysiological methods, standard hematological methods were used, as well as erythrophagocytosis assays and flow cytometry using patient RBCs and plasma, to investigate anti\u2010RBC antibodies, complement activation, and vesiculation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Blood smear analysis revealed significant heterogeneity in RBC size and volume, and the presence of ghost cells, indicating RBC damage. While the patient's RBCs were found opsonized with IgA and IgG autoantibodies, phagocytosis by neutrophils was not induced in vitro, nor did sensitized donor RBCs with patient plasma. Using flow cytometry, we detected vesicles in the patient's plasma and observed patient plasma\u2010induced vesiculation of healthy donor RBC. Patient plasma showed marked complement activation, and the vesicles in the patient plasma were also complement\u2010opsonized, as well as bound by IgA, IgG, and IgM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Based on these findings, we suggest vesiculation of RBCs as evidenced by the presence of vesicles and ghost cells in the patient, and subsequent complement activation induced by the vesicles. This could have driven the aggravation of the disease in this patient, resulting in a fatal outcome.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/trf.18270","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T09:23:14Z","timestamp":1748337794000},"page":"1132-1144","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Vesiculation as potential novel pathogenic mechanism in autoimmune hemolytic anemia"],"prefix":"10.1111","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8739-3577","authenticated-orcid":false,"given":"Esther C. W.","family":"de Boer","sequence":"first","affiliation":[{"name":"Sanquin Research and Landsteiner Laboratory of the Amsterdam University Medical Centers University of Amsterdam  Amsterdam The Netherlands"},{"name":"Department of Pediatric Immunology, Rheumatology, and Infectious Diseases, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam  Amsterdam The Netherlands"},{"name":"Amsterdam Institute for Immunology and Infectious Diseases, Inflammatory Diseases  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Femke V. M.","family":"Mulder","sequence":"additional","affiliation":[{"name":"Sanquin Research and Landsteiner Laboratory of the Amsterdam University Medical Centers University of Amsterdam  Amsterdam The Netherlands"},{"name":"Department of Hematology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6634-5127","authenticated-orcid":false,"given":"Silvia","family":"Neri","sequence":"additional","affiliation":[{"name":"Sanquin Research and Landsteiner Laboratory of the Amsterdam University Medical Centers University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marije","family":"Wiskerke \u2010 van Stuijvenberg","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Diakonessenhuis  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine J. G.","family":"Arts","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, Hematology &amp; Immunology Diakonessenhuis  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Tol","sequence":"additional","affiliation":[{"name":"Sanquin Research and Landsteiner Laboratory of the Amsterdam University Medical Centers University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boukje","family":"Beuger","sequence":"additional","affiliation":[{"name":"Sanquin Research and Landsteiner Laboratory of the Amsterdam University Medical Centers University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthieu C. J.","family":"Bosman","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, Hematology &amp; Immunology Diakonessenhuis  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noortje","family":"Thielen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Diakonessenhuis  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9","family":"van der Griend","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Diakonessenhuis  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia C.","family":"Folman","sequence":"additional","affiliation":[{"name":"Sanquin Diagnostic Services  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masja","family":"de Haas","sequence":"additional","affiliation":[{"name":"Sanquin Research and Landsteiner Laboratory of the Amsterdam University Medical Centers University of Amsterdam  Amsterdam The Netherlands"},{"name":"Department of Hematology Leiden University Medical Center  Leiden The Netherlands"},{"name":"Sanquin Diagnostic Services  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"van Bruggen","sequence":"additional","affiliation":[{"name":"Sanquin Research and Landsteiner Laboratory of the Amsterdam University Medical Centers University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3469-8454","authenticated-orcid":false,"given":"Richard B.","family":"Pouw","sequence":"additional","affiliation":[{"name":"Sanquin Research and Landsteiner Laboratory of the Amsterdam University Medical Centers University of Amsterdam  Amsterdam The Netherlands"},{"name":"Amsterdam Institute for Immunology and Infectious Diseases, Inflammatory Diseases  Amsterdam The Netherlands"},{"name":"Sanquin Diagnostic Services  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine M. I.","family":"Vos","sequence":"additional","affiliation":[{"name":"Amsterdam Institute for Immunology and Infectious Diseases, Inflammatory Diseases  Amsterdam The Netherlands"},{"name":"Sanquin Diagnostic Services  Amsterdam The Netherlands"},{"name":"Department of Hematology, Amsterdam UMC Location University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,12]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2033982"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25084296"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1537-2995.1990.30891020331.x"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1537-2995.1997.37297203520.x"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0609.2003.02846.x"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0300-2977(01)00096-1"},{"key":"e_1_2_10_8_1","article-title":"A case of coombs\u2010negative primary warm autoimmune hemolytic anemia due to IgA antibody that responded well to rituximab and steroids","author":"Rao GGSR","year":"2024","journal-title":"Cureus"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-03-276162"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.4038\/cmj.v58i4.6312"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25212"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1159\/000438964"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1228142"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-10-386805"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V78.4.1105.1105"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.141.5.1602"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(93)90240-8"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.24894"},{"key":"e_1_2_10_19_1","article-title":"Autoimmune hemolytic anemia anti\u2010RBC IgM, but not IgG, antibodies drive in vitro complement activation in flow indirect Antiglobulin test (flow IAT)","author":"Boer ECW","journal-title":"HemaSphere 2024; 8(S1): 2875"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2017004671"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20150019"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.12133"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.5.2861"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/ccr3.203"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V64.5.1000.1000"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0090-1229(81)90213-0"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/trf.17532"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020003077"},{"issue":"14","key":"e_1_2_10_29_1","first-page":"1579","article-title":"Hemolysis in the spleen drives erythrocyte turnover","volume":"136","author":"Klei TRL","year":"2020","journal-title":"Blood"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0042250"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.604738"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2008.07055.x"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2016.04.003"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.26108"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4400946"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.15757"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.4.2329"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-86489-4"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019003809"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7253-1_2"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1537-2995.1987.27187121473.x"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.5.2950"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-022-03569-5"},{"issue":"2","key":"e_1_2_10_44_1","first-page":"124","article-title":"Conventional, high\u2010resolution and imaging flow cytometry: benchmarking performance in characterisation of extracellular vesicles","volume":"9","author":"Botha J","year":"2021","journal-title":"Biomedicine"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.065"}],"container-title":["Transfusion"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/trf.18270","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/trf.18270","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/trf.18270","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T14:21:05Z","timestamp":1789654865000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/trf.18270"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,12]]},"references-count":44,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1111\/trf.18270"],"URL":"https:\/\/doi.org\/10.1111\/trf.18270","archive":["Portico"],"relation":{},"ISSN":["0041-1132","1537-2995"],"issn-type":[{"value":"0041-1132","type":"print"},{"value":"1537-2995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,12]]},"assertion":[{"value":"2025-01-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}