{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T19:33:05Z","timestamp":1792611185323,"version":"4.5.0"},"reference-count":38,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T00:00:00Z","timestamp":1738108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["TropicalMed"],"abstract":"<jats:p>Background: Severe yellow fever (YF) can result in acute liver failure (ALF) and high mortality. The role of therapeutic plasma exchange (TPE) in managing YF-ALF remains unclear. This study evaluated the impact of TPE strategies in severe YF. Methods: This observational case-series study evaluated three groups of patients classified according to treatment: G1 (standard intensive care support [ICS]), G2 (ICS + high-volume-TPE [HV-TPE]), and G3 (ICS + intensive TPE). HV-TPE was performed during 3 consecutive days with extra sessions of one plasma-volume, if necessary, whereas intensive TPE consisted of one plasma volume\/session performed twice daily, with additional fresh frozen plasma infusion. Hemostatic agents, including tranexamic acid, platelets, and cryoprecipitate, were administered as needed. TPE was de-escalated based on clinical and laboratory parameters. The primary outcome was mortality. Results: Sixty-six patients were included (G1: 41, G2: 11, G3: 14). Groups had similar baseline characteristics. Mortality was significantly lower in G3 (14%) compared to G2 (82%) and G1 (85%) (p &lt; 0.001). Additionally, G3 patients showed a higher frequency of undetectable YF viral load. Conclusions: Intensive TPE is a feasible and effective intervention for severe YF, achieving an 84% reduction in mortality. The limitations of our results are the small sample size, observational and single-center study. Further studies are warranted to elucidate intensive TPE\u2019s role in YF management.<\/jats:p>","DOI":"10.3390\/tropicalmed10020039","type":"journal-article","created":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T07:45:12Z","timestamp":1738136712000},"page":"39","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Intensive Therapeutic Plasma Exchange\u2014New Approach to Treat and Rescue Patients with Severe Form of Yellow Fever"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8719-2508","authenticated-orcid":false,"given":"Yeh-Li","family":"Ho","sequence":"first","affiliation":[{"name":"Departamento de Infectologia e Medicina Tropical, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youko","family":"Nukui","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Hematologia, Hemoterapia e Terapia Celular, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula Ribeiro","family":"Villa\u00e7a","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Hematologia, Hemoterapia e Terapia Celular, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Okazaki","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Hematologia, Hemoterapia e Terapia Celular, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelson Hidekazu","family":"Tatsui","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Hematologia, Hemoterapia e Terapia Celular, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas Chaves","family":"Netto","sequence":"additional","affiliation":[{"name":"Departamento de Infectologia e Medicina Tropical, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4190-1334","authenticated-orcid":false,"given":"Daniel","family":"Joelsons","sequence":"additional","affiliation":[{"name":"Departamento de Infectologia e Medicina Tropical, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania Rubia Flores","family":"da Rocha","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Hematologia, Hemoterapia e Terapia Celular, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8887-5060","authenticated-orcid":false,"given":"Fernanda","family":"de Mello Malta","sequence":"additional","affiliation":[{"name":"LIM07, Departamento de Gastroenterologia, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3999-0489","authenticated-orcid":false,"given":"Jo\u00e3o Renato Rebello","family":"Pinho","sequence":"additional","affiliation":[{"name":"LIM07, Departamento de Gastroenterologia, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6311-8036","authenticated-orcid":false,"given":"Aluisio Augusto Cotrim","family":"Segurado","sequence":"additional","affiliation":[{"name":"Departamento de Infectologia e Medicina Tropical, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanderson","family":"Rocha","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Hematologia, Hemoterapia e Terapia Celular, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-000, Brazil"},{"name":"Fundacao Pro-Sangue, Sao Paulo 05403-000, Brazil"},{"name":"Churchill Hospital, Oxford University Hospitals, Oxford OX3 7LE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,29]]},"reference":[{"key":"ref_1","first-page":"tax008","article-title":"Importation of yellow fever into China: Assessing travel patterns","volume":"24","author":"Leong","year":"2017","journal-title":"J. Travel Med."},{"key":"ref_2","unstructured":"Sa\u00fade, S.d.V.e. (2017\/2018). Monitoramento do Per\u00edodo Sazonal da Febre Amarela Brasil\u20132017\/2018."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"340","DOI":"10.15585\/mmwr.mm6711e1","article-title":"Fatal Yellow Fever in Travelers to Brazil, 2018","volume":"67","author":"Hamer","year":"2018","journal-title":"MMWR Morb. Mortal Wkly. Rep."},{"key":"ref_4","unstructured":"WHO (2018). A Global Strategy to Eliminate Yellow Fever Epidemics 2017\u20132026."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/S0065-3527(03)60009-6","article-title":"Pathogenesis and pathophysiology of yellow fever","volume":"60","author":"Monath","year":"2003","journal-title":"Adv. Virus Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/j.jhep.2016.12.003","article-title":"EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure","volume":"66","author":"Wendon","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.jhep.2007.01.010","article-title":"Acute liver failure: Bridging to transplant or recovery--are we there yet?","volume":"46","author":"Singhal","year":"2007","journal-title":"J. Hepatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1002\/hep.30273","article-title":"Liver transplantation for fulminant hepatitis due to yellow fever","volume":"69","author":"Song","year":"2018","journal-title":"Hepatology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2228","DOI":"10.1111\/liv.13914","article-title":"Long-term outcome in patients with acute liver failure","volume":"38","author":"Putignano","year":"2018","journal-title":"Liver Int."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1002\/hep.1840060417","article-title":"Multivariate analysis of prognostic factors in fulminant hepatitis B","volume":"6","author":"Bernuau","year":"1986","journal-title":"Hepatology"},{"key":"ref_11","unstructured":"Sa\u00fade, M.d. (2018). Portaria 2117-Estrat\u00e9gia para Assist\u00eancia em Insufici\u00eancia Hep\u00e1tica Hiperaguda por Febre Amarela."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.cld.2018.01.011","article-title":"Future Approaches and Therapeutic Modalities for Acute Liver Failure","volume":"22","author":"Patel","year":"2018","journal-title":"Clin. Liver Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.jhep.2015.08.018","article-title":"High-volume plasma exchange in patients with acute liver failure: An open randomised controlled trial","volume":"64","author":"Larsen","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"taz040","DOI":"10.1093\/jtm\/taz040","article-title":"Severe yellow fever in Brazil: Clinical characteristics and management","volume":"26","author":"Ho","year":"2019","journal-title":"J. Travel Med."},{"key":"ref_15","unstructured":"Melo, R., Ho, Y., Tatsui, N., Nakamura, M., EK, I., Carvalho, H., Okazaki, E., Villa\u00e7a, P., and Nukui, Y. (November, January 31). Papel da troca plasm\u00e1tica na insufici\u00eancia hep\u00e1tica aguda p\u00f3s infec\u00e7\u00e3o pelo v\u00edrus da febre amarela: Descri\u00e7\u00e3o da experi\u00eancia de um servi\u00e7o quatern\u00e1rio. Proceedings of the HEMO 2018 Congresso Brasileiro de Hematologia, Hemoterapia e Terapia Celular, S\u00e3o Paulo, Brazil."},{"key":"ref_16","unstructured":"Nukui, Y., Ho, Y., Tatsui, N., Nakamura, M., Inoue, E., Maio, K., Junior, A., Villa\u00e7a, P., and Rocha, V. (November, January 31). Papel da troca plasm\u00e1tica na insufici\u00eancia hep\u00e1tica aguda p\u00f3s infec\u00e7\u00e3o pelo v\u00edrus da febre amarela: Descri\u00e7\u00e3o de um caso de sucesso-o que aprendemos e sugest\u00e3o de proposta de tratamento. Proceedings of the HEMO 2018 Congresso Brasileiro de Hematologia, Hemoterapia e Terapia Celular, S\u00e3o Paulo, Brazil."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/s41426-018-0128-8","article-title":"Yellow fever in the diagnostics laboratory","volume":"7","author":"Domingo","year":"2018","journal-title":"Emerg. Microbes Infect."},{"key":"ref_18","unstructured":"Walker, G.A., and Shostak, J. (2010). Common Statistical Methods for Clinical Research with SAS Examples, SAS Institute. [3rd ed.]."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.antiviral.2012.12.002","article-title":"Experimental therapies for yellow fever","volume":"97","author":"Julander","year":"2013","journal-title":"Antivir. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"tay097","DOI":"10.1093\/jtm\/tay097","article-title":"Pandemic yellow fever: A potential threat to global health via travelers","volume":"25","author":"Gubler","year":"2018","journal-title":"J. Travel Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.trstmh.2006.04.001","article-title":"Clinical and epidemiological characteristics of yellow fever in Brazil: Analysis of reported cases 1998\u20132002","volume":"101","author":"Tuboi","year":"2007","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1086\/425016","article-title":"Activation of the cytokine network and unfavorable outcome in patients with yellow fever","volume":"190","author":"Sakho","year":"2004","journal-title":"J. Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e70099","DOI":"10.1002\/jmv.70099","article-title":"Systems Immunology Approaches to Understanding Immune Responses in Acute Infection of Yellow Fever Patients","volume":"96","author":"Costa","year":"2024","journal-title":"J. Med. Virol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/S1473-3099(19)30125-2","article-title":"Predictors of mortality in patients with yellow fever: An observational cohort study","volume":"19","author":"Kallas","year":"2019","journal-title":"Lancet Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1093\/infdis\/jiac435","article-title":"Viral Kinetics in Sylvatic Yellow Fever Cases","volume":"227","author":"Thomazella","year":"2023","journal-title":"J. Infect. Dis."},{"key":"ref_26","first-page":"149","article-title":"Guidelines on the Use of Therapeutic Apheresis in Clinical Practice-Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Seventh Special Issue","volume":"31","author":"Schwartz","year":"2016","journal-title":"J. Clin. Apher."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.jhep.2015.09.010","article-title":"High volume plasma exchange in acute liver failure: Dampening the inflammatory cascade?","volume":"64","author":"Karvellas","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/s11011-013-9403-5","article-title":"Efficacy of liver assisting in patients with hepatic encephalopathy with special focus on plasma exchange","volume":"28","author":"Stenbog","year":"2013","journal-title":"Metab. Brain Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1097\/00003246-199805000-00021","article-title":"Removal of endotoxin and cytokines by plasma exchange in patients with acute hepatic failure","volume":"26","author":"Iwai","year":"1998","journal-title":"Crit. Care Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2525","DOI":"10.1056\/NEJMra1208937","article-title":"Acute liver failure","volume":"369","author":"Bernal","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1111\/j.1572-0241.2001.03706.x","article-title":"Effects of high-volume plasmapheresis on ammonia, urea, and amino acids in patients with acute liver failure","volume":"96","author":"Clemmesen","year":"2001","journal-title":"Am. J. Gastroenterol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1002\/jca.20064","article-title":"The effect of total plasma exchange on fulminant hepatic failure","volume":"21","author":"Akdogan","year":"2006","journal-title":"J. Clin. Apher."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"176","DOI":"10.3201\/eid2401.171310","article-title":"Yellow Fever Virus RNA in Urine and Semen of Convalescent Patient, Brazil","volume":"24","author":"Barbosa","year":"2018","journal-title":"Emerg. Infect. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e190033","DOI":"10.1590\/0074-02760190033","article-title":"Lipase and factor V (but not viral load) are prognostic factors for the evolution of severe yellow fever cases","volume":"114","author":"Casadio","year":"2019","journal-title":"Mem\u00f3rias Inst. Oswaldo Cruz"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1111\/his.13904","article-title":"Yellow fever and orthotopic liver transplantation: New insights from the autopsy room for an old but re-emerging disease","volume":"75","author":"Cunha","year":"2019","journal-title":"Histopathology"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Giugni, F.R., Aiello, V.D., Faria, C.S., Pour, S.Z., Cunha, M.D.P., Giugni, M.V., Pinesi, H.T., Ledesma, F.L., Morais, C.E., and Ho, Y.L. (2023). Understanding yellow fever-associated myocardial injury: An autopsy study. EBioMedicine, 96.","DOI":"10.1016\/j.ebiom.2023.104810"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"de Sousa, F.T.G., Warnes, C.M., Manuli, E.R., Tjang, L.V., Carneiro, P.H., Maria de Oliveira Pinto, L., Ng, A., Bhat, S., Zambrana, J.V., and D\u2019Elia Zanella, L. (2024). Yellow fever disease severity and endothelial dysfunction are associated with elevated serum levels of viral NS1 protein and syndecan-1. EBioMedicine, 109.","DOI":"10.1016\/j.ebiom.2024.105409"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"32648","DOI":"10.1073\/pnas.2014096117","article-title":"Consumptive coagulopathy of severe yellow fever occurs independently of hepatocellular tropism and massive hepatic injury","volume":"117","author":"Bailey","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Tropical Medicine and Infectious Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2414-6366\/10\/2\/39\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:38:13Z","timestamp":1759919893000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2414-6366\/10\/2\/39"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,29]]},"references-count":38,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["tropicalmed10020039"],"URL":"https:\/\/doi.org\/10.3390\/tropicalmed10020039","relation":{},"ISSN":["2414-6366"],"issn-type":[{"value":"2414-6366","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,29]]}}}