{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T10:45:35Z","timestamp":1772621135385,"version":"3.50.1"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"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>\n                    Clostridium perfringens (CP), an anaerobic Gram-positive bacterium, is commonly associated with food poisoning and gas gangrene. In rare instances, it can cause fatal massive intravascular hemolysis (MIH), a condition associated with exceedingly high mortality that poses a serious clinical challenge. A retrospective analysis was performed using a fatal case of T-lymphoblastic lymphoma\/leukemia complicated by CP-associated acute hemolysis treated at our center in November 2024 and case reports of CP-associated MIH in hematologic patients from January 1987 to September 2025. A total of 23 eligible cases from our institution and published literature were included. The cohort consisted of 60.8% (\n                    <jats:italic>n<\/jats:italic>\n                    = 14) male patients, with a mean age of 45.87 \u00b1 17.94 years. All patients presented with fever, hematuria was observed in 69.5% of patients, shock in 78.2%, and altered mental status (AMS) in 60.8%. The overall mortality rate was 73.9%, with a median survival time of 13.5 (6, 24) hours among non-survivors. AMS was identified as an independent risk factor for mortality (OR = 14.03, 95% CI: 1.19\u2013165.08,\n                    <jats:italic>p<\/jats:italic>\n                    = 0.036). The pathogenic cascade, conceptualized as a \u201cdouble-hit\u201d model, is triggered by the synergistic action of \u03b1-toxin and \u03b8-toxin. Together, they induce fulminant intravascular hemolysis and a systemic inflammatory response, culminating in organ injury. Although no specific therapeutics are available, immediate empirical combination antibiotic therapy (such as penicillin with clindamycin) is paramount. Adjunctive measures, including intensive care support and toxin removal strategies, are essential components of care. This study emphasizes the severity of CP-MIH in hematologic patients and identifies AMS as a key prognostic marker, underscoring the need for early intervention and further research into rapid diagnostics and targeted treatments.\n                  <\/jats:p>","DOI":"10.3389\/fmed.2026.1726461","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T05:42:04Z","timestamp":1772602924000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical characteristics and prognostic factors of Clostridium perfringens infection complicated by massive intravascular hemolysis in patients with hematologic diseases: a retrospective case series study"],"prefix":"10.3389","volume":"13","author":[{"given":"Weixiang","family":"Lin","sequence":"first","affiliation":[{"name":"Key Laboratory of Xiamen for Diagnosis and Treatment of Hematologic Malignancy, Department of Hematology, The First Affiliated Hospital of Xiamen University, Xiamen Hematology Medical Quality Control Center","place":["Xiamen, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Feng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Xiamen for Diagnosis and Treatment of Hematologic Malignancy, Department of Hematology, The First Affiliated Hospital of Xiamen University, Xiamen Hematology Medical Quality Control Center","place":["Xiamen, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhihong","family":"Fang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Xiamen for Diagnosis and Treatment of Hematologic Malignancy, Department of Hematology, The First Affiliated Hospital of Xiamen University, Xiamen Hematology Medical Quality Control Center","place":["Xiamen, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"769","DOI":"10.3390\/antibiotics13080769","article-title":"Clostridioides difficile infection: use of inflammatory biomarkers and hemogram-derived ratios to predict mortality risk in hospitalized patients.","volume":"13","author":"Scarlata","year":"2024","journal-title":"Antibiotics."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.2147\/imcrj.S553444","article-title":"Familial cluster of foodborne botulism associated with homemade dairy products: a case series.","volume":"18","author":"Saravani","year":"2025","journal-title":"Int Med Case Rep J."},{"key":"B3","doi-asserted-by":"publisher","first-page":"824","DOI":"10.3390\/microorganisms11040824","article-title":"Clinical and microbiological features of fulminant haemolysis caused by Clostridium perfringens bacteraemia: unknown pathogenesis.","volume":"11","author":"Suzaki","year":"2023","journal-title":"Microorganisms."},{"key":"B4","doi-asserted-by":"publisher","first-page":"e0429923","DOI":"10.1128\/spectrum.04299-23","article-title":"Risk factors and molecular epidemiology of intestinal colonization by carbapenem-resistant Gram-negative bacteria in patients with hematological diseases: a multicenter case\u2013control study.","volume":"12","author":"Hu","year":"2024","journal-title":"Microbiol Spectr."},{"key":"B5","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1111\/1469-0691.12462","article-title":"Clinical characteristics and outcomes of clostridial bacteraemia in cancer patients.","volume":"20","author":"Hammond","year":"2014","journal-title":"Clin Microbiol. Infect."},{"key":"B6","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1002\/jso.2930350104","article-title":"Massive hemolysis in Clostridium perfringens infections.","volume":"35","author":"Becker","year":"1987","journal-title":"J Surg Oncol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1111\/j.1365-2257.1992.tb01074.x","article-title":"Clostridium perfringens septicaemia and massive intravascular haemolysis as a terminal complication of autologous bone marrow transplant.","volume":"14","author":"Ifthikaruddin","year":"1992","journal-title":"Clin Lab Haematol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1055\/s-2008-1058704","article-title":"[Acute Intravasal Hemolysis in Clostridium perfringens Sepsis. Differential Diagnosis of Hemolytic Episodes].","volume":"119","author":"Strobel","year":"1994","journal-title":"Dtsch Med Wochenschr."},{"key":"B9","first-page":"221, 361","article-title":"Photo quiz. Hemolysis induced by Clostridium perfringens.","volume":"22","author":"Singh","year":"1996","journal-title":"Clin Infect Dis."},{"key":"B10","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/s0735-6757(97)90088-7","article-title":"Clostridium perfringens septicemia with massive hemolysis in a patient with Hodgkin\u2019s lymphoma.","volume":"15","author":"Singer","year":"1997","journal-title":"Am J Emerg Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1002\/ajh.10106","article-title":"Spontaneous gas gangrene in malignant lymphoma: an underreported complication?","volume":"70","author":"Garc\u00eda-Su\u00e1rez","year":"2002","journal-title":"Am J Hematol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"2157","DOI":"10.1080\/10428190410001697331","article-title":"Massive intravascular hemolysis: a fatal complication of Clostridium Perfringens septicemia in a patient with acute myeloid leukemia.","volume":"45","author":"Vaiopoulos","year":"2004","journal-title":"Leuk Lymphoma."},{"key":"B13","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1080\/10428190500032687","article-title":"Massive intravascular hemolysis: a fatal complication of Clostridium perfringens septicemia in a patient with acute lymphoblastic leukemia.","volume":"46","author":"Pirrotta","year":"2005","journal-title":"Leuk Lymphoma."},{"key":"B14","doi-asserted-by":"publisher","first-page":"2016","DOI":"10.1378\/chest.07-0853","article-title":"Massive intravascular hemolysis and a rapidly fatal outcome.","volume":"132","author":"Kapoor","year":"2007","journal-title":"Chest."},{"key":"B15","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1159\/000106763","article-title":"Puerperal Clostridium perfringens sepsis in a patient with granulocytopenia.","volume":"65","author":"Nadisauskiene","year":"2008","journal-title":"Gynecol Obstet Invest."},{"key":"B16","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1111\/j.1442-200X.2011.03436.x","article-title":"Fulminant Clostridium perfringens sepsis during induction chemotherapy in childhood leukemia.","volume":"54","author":"Salvador","year":"2012","journal-title":"Pediatr Int."},{"key":"B17","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1111\/bjh.12745","article-title":"Intravascular haemolysis secondary to Clostridium perfringens in a patient with acute myeloid leukaemia undergoing allogeneic stem cell transplantation.","volume":"165","author":"Renaudon-Smith","year":"2014","journal-title":"Br J Haematol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"6549268","DOI":"10.1155\/2016\/6549268","article-title":"Acute hemolysis with renal failure due to clostridium bacteremia in a patient with AML.","volume":"2016","author":"Medrano-Juarez","year":"2016","journal-title":"Case Rep Infect Dis."},{"key":"B19","doi-asserted-by":"publisher","first-page":"e92","DOI":"10.5546\/aap.2017.eng.e92","article-title":"A fatal Clostridium perfringens infection with hemolysis after chemotherapy in an adolescent.","volume":"115","author":"Kukul","year":"2017","journal-title":"Arch Argent Pediatr."},{"key":"B20","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1097\/ipc.0000000000000630","article-title":"Clostridium perfringens infection with massive hemolysis: a rare survivor. case report and literature review.","volume":"26","author":"Wilson","year":"2018","journal-title":"Infect Dis Clin Pract."},{"key":"B21","doi-asserted-by":"publisher","first-page":"2193","DOI":"10.1093\/cid\/ciz042","article-title":"48-year-old male with febrile neutropenia and massive hemolysis.","volume":"69","author":"Jakharia","year":"2019","journal-title":"Clin Infect Dis."},{"key":"B22","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1007\/s12185-020-03060-z","article-title":"Clostridium perfringens sepsis in three patients with acute leukemia and review of the literature.","volume":"113","author":"Liu","year":"2021","journal-title":"Int J Hematol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"2813","DOI":"10.1007\/s00277-022-05010-7","article-title":"Acute fulminant intravascular hemolysis induced by Clostridium perfringens in a symptomatic multiple myeloma patient under immuno-chemotherapy.","volume":"101","author":"Yamamoto","year":"2022","journal-title":"Ann Hematol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"e108","DOI":"10.1093\/labmed\/lmac135","article-title":"Case of fatal Clostridium perfringens sepsis with massive hemolysis in the setting of a coincidental platelet transfusion.","volume":"54","author":"Boyd","year":"2023","journal-title":"Lab Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"e1545","DOI":"10.3760\/cma.j.cmcr20240424-00648","article-title":"A case of hemolytic Clostridium perfringens in acute leukemia myelosuppressive stage.","volume":"6","author":"Xia","year":"2024","journal-title":"Chin Med Care Repository."},{"key":"B26","doi-asserted-by":"publisher","first-page":"e77122","DOI":"10.7759\/cureus.77122","article-title":"Clostridium perfringens sepsis complicated by hepatic abscess following intensive chemotherapy in mixed-phenotype acute leukemia.","volume":"17","author":"Baptista","year":"2025","journal-title":"Cureus."},{"key":"B27","first-page":"343","article-title":"Clostridium perfringens septicaemia with massive intravascular haemolysis: a case report and review of the literature.","volume":"68","author":"van Bunderen","year":"2010","journal-title":"Neth J Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"e955","DOI":"10.1016\/j.ijid.2013.03.001","article-title":"Clinical significance and outcomes of Clostridium perfringens bacteremia\u2013a 10-year experience at a tertiary care hospital.","volume":"17","author":"Yang","year":"2013","journal-title":"Int J Infect Dis."},{"key":"B29","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1016\/j.mcp.2007.08.001","article-title":"Real-time quantitative pcr for rapid detection of Clostridium perfringens.","volume":"25","author":"Li","year":"2011","journal-title":"J Chin Pract Diagn Ther."},{"key":"B30","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1177\/0885066613498043","article-title":"Massive intravascular hemolysis from Clostridium perfringens septicemia: a review.","volume":"29","author":"Simon","year":"2014","journal-title":"J Intensive Care Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"713509","DOI":"10.3389\/fmicb.2021.713509","article-title":"Pathogenic characterization of Clostridium Perfringens strains isolated from patients with massive intravascular hemolysis.","volume":"12","author":"Suzaki","year":"2021","journal-title":"Front Microbiol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"2341968","DOI":"10.1080\/22221751.2024.2341968","article-title":"Unveiling the pathogenic mechanisms of Clostridium perfringens toxins and virulence factors.","volume":"13","author":"Camargo","year":"2024","journal-title":"Emerg Microbes Infect."},{"key":"B33","doi-asserted-by":"publisher","first-page":"e2020185","DOI":"10.4322\/acr.2020.185","article-title":"Sudden death caused by Clostridium perfringens sepsis presenting as massive intravascular hemolysis.","volume":"10","author":"Chinen","year":"2020","journal-title":"Autops Case Rep."},{"key":"B34","doi-asserted-by":"publisher","first-page":"102202","DOI":"10.1016\/j.anaerobe.2020.102202","article-title":"Clinical relevance of clostridium bacteremia: an 8-year retrospective study.","volume":"63","author":"Stabler","year":"2020","journal-title":"Anaerobe."},{"key":"B35","doi-asserted-by":"publisher","first-page":"e363","DOI":"10.1128\/jcm.00363-20","article-title":"Diagnostic accuracy of nucleic acid amplification-based assays for clostridium perfringens-associated diseases: a systematic review and meta-analysis.","volume":"58","author":"Chen","year":"2020","journal-title":"J Clin Microbiol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.ijmmb.2021.03.017","article-title":"Sequencing of Clostridium perfringens toxin genes (cpa, etx, iap) from Iraqi hospitals and detection by PCR of the genes encoding resistance to metronidazole, tetracycline, and clindamycin.","volume":"39","author":"Al-Shukri","year":"2021","journal-title":"Indian J Med Microbiol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1007\/s11908-010-0127-y","article-title":"Clostridial myonecrosis: new insights in pathogenesis and management.","volume":"12","author":"Bryant","year":"2010","journal-title":"Curr Infect Dis Rep."},{"key":"B38","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1128\/aac.31.2.213","article-title":"Effect of antibiotics on toxin production and viability of Clostridium perfringens.","volume":"31","author":"Stevens","year":"1987","journal-title":"Antimicrob Agents Chemother."},{"key":"B39","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1007\/s13730-024-00857-3","article-title":"Clostridium perfringens-induced massive hemolysis treatment with blood purification to target toxins: a case report.","volume":"13","author":"Reffo","year":"2024","journal-title":"CEN Case Rep."},{"key":"B40","doi-asserted-by":"publisher","first-page":"2213","DOI":"10.2169\/internalmedicine.50.5829","article-title":"Successful treatment of necrotizing fasciitis in an upper extremity caused by Clostridium perfringens after bone marrow transplantation.","volume":"50","author":"Ito","year":"2011","journal-title":"Intern Med."},{"key":"B41","doi-asserted-by":"publisher","first-page":"454","DOI":"10.3390\/pathogens13060454","article-title":"Purinergic receptor antagonists inhibit hemolysis induced by Clostridium perfringens alpha toxin.","volume":"13","author":"Guo","year":"2024","journal-title":"Pathogens."},{"key":"B42","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1093\/intimm\/dxu081","article-title":"Therapeutic uses of anti-interleukin-6 receptor antibody.","volume":"27","author":"Kang","year":"2015","journal-title":"Int Immunol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"179","DOI":"10.3389\/fphar.2020.00179","article-title":"Amentoflavone attenuates Clostridium perfringens gas gangrene by targeting alpha-toxin and perfringolysin O.","volume":"11","author":"Liu","year":"2020","journal-title":"Front Pharmacol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"lxad273","DOI":"10.1093\/jambio\/lxad273","article-title":"Repurposing rabeprazole sodium as an anti-Clostridium perfringens drug by inhibiting perfringolysin O.","volume":"134","author":"Wang","year":"2023","journal-title":"J Appl Microbiol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"eadf8782","DOI":"10.1126\/sciadv.adf8782","article-title":"Gut-targeted nanoparticles deliver specifically targeted antimicrobial peptides against Clostridium perfringens infections.","volume":"9","author":"Xu","year":"2023","journal-title":"Sci Adv."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1726461\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T05:42:06Z","timestamp":1772602926000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1726461\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,4]]},"references-count":45,"alternative-id":["10.3389\/fmed.2026.1726461"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1726461","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,4]]},"article-number":"1726461"}}