{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T23:15:57Z","timestamp":1784762157328,"version":"3.55.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Atypical hemolytic uremic syndrome (aHUS) is a complement-associated thrombotic microangiopathy (TMA). Thalassemia is a hemolytic anemia triggered by defects in the beta-globin gene. Mutations in the complement factor H (CFH) gene are associated with the development of aHUS; however, CFH gene mutations coexisting with thalassemia have rarely been reported. CFH gene mutations are susceptibility factors that can trigger complement overactivation during pregnancy. When aHUS is combined with thalassemia, large amounts of hemoglobin are released from fragmented erythrocytes, leading to amplification of the complement cascade and resulting in a \u201ctwo-hit\u201d mechanism that may affect the efficacy of C5 inhibitors. Here, we report a case of pregnancy-associated aHUS in a patient with thalassemia and a CFH gene mutation. After admission to the hospital, plasmapheresis and hemodialysis were used to treat TMA. Following confirmation of aHUS, eculizumab was initiated immediately, and the erythroid maturation agent luspatercept was added for the treatment of thalassemia. The patient was weaned off hemodialysis, and there was no recurrence of aHUS during the follow-up period. This diagnostic and therapeutic approach may provide a new strategy for the use of C5 inhibitors to treat patients with aHUS and thalassemia.<\/jats:p>","DOI":"10.3389\/fmed.2026.1659141","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T13:42:31Z","timestamp":1777297351000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Atypical hemolytic uremic syndrome in a patient with thalassemia and a CFH gene mutation: a case report"],"prefix":"10.3389","volume":"13","author":[{"given":"Jing","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Nephrology, NHC Key Laboratory of Pulmonary Immunological Disease, Guizhou Provincial Key Laboratory of Pathogenesis and Prevention of Common Chronic Diseases Research, Guizhou Provincial People's Hospital","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, NHC Key Laboratory of Pulmonary Immunological Disease, Guizhou Provincial Key Laboratory of Pathogenesis and Prevention of Common Chronic Diseases Research, Guizhou Provincial People's Hospital","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, NHC Key Laboratory of Pulmonary Immunological Disease, Guizhou Provincial Key Laboratory of Pathogenesis and Prevention of Common Chronic Diseases Research, Guizhou Provincial People's Hospital","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, NHC Key Laboratory of Pulmonary Immunological Disease, Guizhou Provincial Key Laboratory of Pathogenesis and Prevention of Common Chronic Diseases Research, Guizhou Provincial People's Hospital","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, NHC Key Laboratory of Pulmonary Immunological Disease, Guizhou Provincial Key Laboratory of Pathogenesis and Prevention of Common Chronic Diseases Research, Guizhou Provincial People's Hospital","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Nephrology, NHC Key Laboratory of Pulmonary Immunological Disease, Guizhou Provincial Key Laboratory of Pathogenesis and Prevention of Common Chronic Diseases Research, Guizhou Provincial People's Hospital","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zha","sequence":"additional","affiliation":[{"name":"Department of Nephrology, NHC Key Laboratory of Pulmonary Immunological Disease, Guizhou Provincial Key Laboratory of Pathogenesis and Prevention of Common Chronic Diseases Research, Guizhou Provincial People's Hospital","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,27]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1182\/blood.2022017860","article-title":"How I diagnose and treat atypical hemolytic uremic syndrome","volume":"141","author":"Fakhouri","year":"2023","journal-title":"Blood"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1111\/1744-9987.12763","article-title":"Atypical hemolytic-uremic syndrome: an update on pathophysiology, diagnosis, and treatment","volume":"23","author":"Raina","year":"2019","journal-title":"Ther Apher Dial"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.molimm.2015.03.246","article-title":"Atypical aHUS: state of the art","volume":"67","author":"Nester","year":"2015","journal-title":"Mol Immunol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1424380","DOI":"10.3389\/fped.2024.1424380","article-title":"Case report: C3 deficiency in two siblings","volume":"12","author":"Bernacchia","year":"2024","journal-title":"Front Pediatr"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1182\/blood-2013-03-489245","article-title":"Complement activation by heme as a secondary hit for atypical hemolytic uremic syndrome","volume":"122","author":"Frimat","year":"2013","journal-title":"Blood"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"2392","DOI":"10.1681\/ASN.2006080811","article-title":"Differential impact of complement mutations on clinical characteristics in atypical hemolytic uremic syndrome","volume":"18","author":"Sellier-Leclerc","year":"2007","journal-title":"J Am Soc Nephrol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"14496","DOI":"10.3390\/ijms241914496","article-title":"Underlying genetics of aHUS: which connection with outcome and treatment discontinuation?","volume":"24","author":"Spasiano","year":"2023","journal-title":"Int J Mol Sci"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"9677","DOI":"10.3390\/ijms22189677","article-title":"Pathomechanisms of immunological disturbances in \u03b2-thalassemia","volume":"22","author":"Gluba-Brz\u00f3zka","year":"2021","journal-title":"Int J Mol Sci"},{"key":"ref9","doi-asserted-by":"publisher","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"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1038\/s42003-023-04535-5","article-title":"Oxidized hemoglobin triggers polyreactivity and autoreactivity of human IgG via transfer of heme","volume":"6","author":"Planchais","year":"2023","journal-title":"Commun Biol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"427","DOI":"10.3390\/jcm10030427","article-title":"Linking labile Heme with thrombosis","volume":"10","author":"Hopp","year":"2021","journal-title":"J Clin Med"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"5543","DOI":"10.4049\/jimmunol.179.8.5543","article-title":"Hematin promotes complement alternative pathway-mediated deposition of C3 activation fragments on human erythrocytes: potential implications for the pathogenesis of anemia in malaria","volume":"179","author":"Pawluczkowycz","year":"2007","journal-title":"J Immunol"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1007\/s10157-016-1276-6","article-title":"Joint Committee for the Revision of clinical guides of atypical hemolytic uremic syndrome in Japan. Clinical guides for atypical hemolytic uremic syndrome in Japan","volume":"20","author":"Kato","year":"2016","journal-title":"Clin Exp Nephrol"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1038\/nrneph.2010.155","article-title":"New insights into postrenal transplant hemolytic uremic syndrome","volume":"7","author":"Zuber","year":"2011","journal-title":"Nat Rev Nephrol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1189","DOI":"10.1016\/j.mayocp.2016.05.015","article-title":"Thrombotic microangiopathy care pathway: a consensus statement for the Mayo Clinic complement alternative pathway-thrombotic Microangiopathy (CAP-TMA) disease-oriented group","volume":"91","author":"Go","year":"2016","journal-title":"Mayo Clin Proc"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1007\/s00467-015-3076-8","article-title":"An international consensus approach to the management of atypical hemolytic uremic syndrome in children","volume":"31","author":"Loirat","year":"2016","journal-title":"Pediatr Nephrol"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1038\/s41581-021-00424-4","article-title":"Thrombotic microangiopathy in aHUS and beyond: clinical clues from complement genetics","volume":"17","author":"Fakhouri","year":"2021","journal-title":"Nat Rev Nephrol"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1038\/ng.2590","article-title":"Recessive mutations in DGKE cause atypical hemolytic-uremic syndrome","volume":"45","author":"Lemaire","year":"2013","journal-title":"Nat Genet"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1348","DOI":"10.3389\/fimmu.2020.01348","article-title":"The relevance of the MCP risk polymorphism to the outcome of aHUS associated with C3 mutations. A case report","volume":"11","author":"Lumbreras","year":"2020","journal-title":"Front Immunol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1007\/s00467-010-1556-4","article-title":"aHUS caused by complement dysregulation: new therapies on the horizon","volume":"26","author":"Waters","year":"2011","journal-title":"Pediatr Nephrol"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1016\/j.chest.2017.03.055","article-title":"Expert statements on the standard of Care in Critically ill Adult Patients with Atypical Hemolytic Uremic Syndrome","volume":"152","author":"Azoulay","year":"2017","journal-title":"Chest"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"25","DOI":"10.3904\/kjim.2019.388","article-title":"Consensus regarding diagnosis and management of atypical hemolytic uremic syndrome","volume":"35","author":"Lee","year":"2020","journal-title":"Korean J Intern Med"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"27","DOI":"10.3265\/Nefrologia.pre2012.Nov.11781","article-title":"An update for atypical haemolytic uraemic syndrome: diagnosis and treatment. A consensus document","volume":"33","author":"Campistol","year":"2013","journal-title":"Nefrologia"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1264310","DOI":"10.3389\/fmed.2023.1264310","article-title":"Recommendations for the individualised management of atypical hemolytic uremic syndrome in adults","volume":"10","author":"\u00c1vila","year":"2023","journal-title":"Front Med (Lausanne)"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1681\/ASN.2012090884","article-title":"European working party on complement genetics in renal diseases. Combined complement gene mutations in atypical hemolytic uremic syndrome influence clinical phenotype","volume":"24","author":"Bresin","year":"2013","journal-title":"J Am Soc Nephrol"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1681\/ASN.2019050515","article-title":"CFHR gene variations provide insights in the pathogenesis of the kidney diseases atypical hemolytic uremic syndrome and C3 Glomerulopathy","volume":"31","author":"Zipfel","year":"2020","journal-title":"J Am Soc Nephrol"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1016\/j.kint.2019.05.014","article-title":"Severe and malignant hypertension are common in primary atypical hemolytic uremic syndrome","volume":"96","author":"Cavero","year":"2019","journal-title":"Kidney Int"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1007\/s10157-018-1609-8","article-title":"Safety and effectiveness of eculizumab for adult patients with atypical hemolytic-uremic syndrome in Japan: interim analysis of post-marketing surveillance","volume":"23","author":"Kato","year":"2019","journal-title":"Clin Exp Nephrol"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"2185","DOI":"10.1182\/blood.2021012037","article-title":"Functional characterization of 105 factor H variants associated with aHUS: lessons for variant classification","volume":"138","author":"Mart\u00edn Merinero","year":"2021","journal-title":"Blood"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"2438","DOI":"10.1182\/blood.2020009280","article-title":"Eculizumab discontinuation in children and adults with atypical hemolytic-uremic syndrome: a prospective multicenter study","volume":"137","author":"Fakhouri","year":"2021","journal-title":"Blood"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"615748","DOI":"10.3389\/fimmu.2021.615748","article-title":"Deregulation of factor H by factor H-related protein 1 depends on sialylation of host surfaces","volume":"12","author":"Dopler","year":"2021","journal-title":"Front Immunol"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"2075","DOI":"10.1093\/ckj\/sfab005","article-title":"Eculizumab discontinuation in atypical haemolytic uraemic syndrome: TMA recurrence risk and renal outcomes","volume":"14","author":"Ariceta","year":"2021","journal-title":"Clin Kidney J"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"50","DOI":"10.2215\/CJN.06440616","article-title":"Pathogenic variants in complement genes and risk of atypical hemolytic uremic syndrome relapse after Eculizumab discontinuation","volume":"12","author":"Fakhouri","year":"2017","journal-title":"Clin J Am Soc Nephrol"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1136\/jmg.2005.030783","article-title":"The development of atypical haemolytic-uraemic syndrome is influenced by susceptibility factors in factor H and membrane cofactor protein: evidence from two independent cohorts","volume":"42","author":"Fremeaux-Bacchi","year":"2005","journal-title":"J Med Genet"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1016\/j.kint.2016.10.005","article-title":"Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a \"kidney disease: improving global outcomes\" (KDIGO) controversies conference","volume":"91","author":"Goodship","year":"2017","journal-title":"Kidney Int"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"670727","DOI":"10.3389\/fgene.2021.670727","article-title":"CFH and CFHR copy number variations in C3 Glomerulopathy and immune complex-mediated Membranoproliferative glomerulonephritis","volume":"12","author":"Piras","year":"2021","journal-title":"Front Genet"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1016\/j.molimm.2015.06.021","article-title":"Complement factor H, FHR-3 and FHR-1 variants associate in an extended haplotype conferring increased risk of atypical hemolytic uremic syndrome","volume":"67","author":"Bernab\u00e9u-Herrero","year":"2015","journal-title":"Mol Immunol"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.ejim.2015.10.003","article-title":"Development of a new disease severity scoring system for patients with non-transfusion-dependent thalassemia","volume":"28","author":"Cappellini","year":"2016","journal-title":"Eur J Intern Med"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/j.molmed.2014.01.001","article-title":"Complement activation in malaria: friend or foe?","volume":"20","author":"Biryukov","year":"2014","journal-title":"Trends Mol Med"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1016\/j.ccc.2019.11.004","article-title":"Typical and atypical hemolytic uremic syndrome in the critically ill","volume":"36","author":"Manrique-Caballero","year":"2020","journal-title":"Crit Care Clin"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"831","DOI":"10.2215\/CJN.0000000000000198","article-title":"Hemolytic uremic syndrome: a question of terminology","volume":"18","author":"Schwotzer","year":"2023","journal-title":"Clin J Am Soc Nephrol"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1038\/ni.1923","article-title":"Complement: a key system for immune surveillance and homeostasis","volume":"11","author":"Ricklin","year":"2010","journal-title":"Nat Immunol"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1659141\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T13:42:33Z","timestamp":1777297353000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1659141\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,27]]},"references-count":42,"alternative-id":["10.3389\/fmed.2026.1659141"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1659141","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,27]]},"article-number":"1659141"}}