{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T16:04:11Z","timestamp":1788278651233,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.pntd.0013106","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T00:00:00Z","timestamp":1749081600000}}],"reference-count":32,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T00:00:00Z","timestamp":1747872000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Key R&D Program of China","award":["2022YFC2305100"],"award-info":[{"award-number":["2022YFC2305100"]}]},{"name":"the National Science and Technology Major Project of China","award":["grant 92169121"],"award-info":[{"award-number":["grant 92169121"]}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec013\">\n<jats:title>Background<\/jats:title>\n<jats:p>Hemorrhagic manifestations are highly prevalent in severe fever with thrombocytopenia syndrome (SFTS) patients and are significantly associated with fatal outcomes. In this study, we investigated the dynamic changes of activated partial thromboplastin time (APTT) and their association with mortality in SFTS patients.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec014\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We conducted a retrospective study analyzing clinical data from SFTS patients admitted to our hospital between April 2017 and June 2024. The dynamic changes of APTT and their association with clinical outcomes were analyzed.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec015\">\n<jats:title>Results<\/jats:title>\n<jats:p>A total of 788 SFTS patients were enrolled in this study, among whom 96 (12.18%) died during hospitalization. Multivariate logistic regression identified prolonged APTT as an independent predictor of mortality, along with older age, neurological symptoms, higher viral load, and elevated creatinine levels. Prolonged APTT was observed in 568(72.08%) patients upon admission and was associated with the development of neurological symptoms, bleeding, intensive care unit (ICU) transfer, and mortality. APTT\u22652.0 times the upper limit of normal (ULN) was associated with significantly higher mortality (55%) and an increased likelihood of ICU transfer (10%). Restricted cubic splines (RCS) analysis revealed that when the APTT level exceeded specific thresholds (49.86s upon admission and 53.61s at the peak during hospitalization), the predicted mortality of patients with SFTS increased with rising APTT levels. Kinetic analysis showed that APTT levels exhibited a declining trend during hospitalization and returned to the normal range by the 6th day in the survival group, while it gradually increased, reaching its peak on the 3rd day and then gradually decreased in the non-survival group.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec016\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Prolonged APTT was prevalent among SFTS patients and was significantly associated with higher mortality. Monitoring APTT upon admission and its dynamic changes during hospitalization is recommended to enhance the management of SFTS patients.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pntd.0013106","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T17:45:41Z","timestamp":1747935941000},"page":"e0013106","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Dynamic changes of activated partial thromboplastin time and correlation with mortality in patients with severe fever with thrombocytopenia syndrome: A retrospective cohort study"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5060-7121","authenticated-orcid":true,"given":"Huan","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sisi","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9176-8856","authenticated-orcid":true,"given":"Xin","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,5,22]]},"reference":[{"issue":"16","key":"pntd.0013106.ref001","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1056\/NEJMoa1010095","article-title":"Fever with thrombocytopenia associated with a novel bunyavirus in China","volume":"364","author":"X-J Yu","year":"2011","journal-title":"N Engl J Med"},{"key":"pntd.0013106.ref002","first-page":"101133","article-title":"Global epidemiology of severe fever with thrombocytopenia syndrome virus in human and animals: a systematic review and meta-analysis","volume":"48","author":"H Cui","year":"2024","journal-title":"Lancet Reg Health West Pac"},{"issue":"11","key":"pntd.0013106.ref003","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.3201\/eid2411.170756","article-title":"Severe Fever with Thrombocytopenia Syndrome Virus Infection, South Korea, 2010","volume":"24","author":"YR Kim","year":"2018","journal-title":"Emerg Infect Dis"},{"issue":"6","key":"pntd.0013106.ref004","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1093\/infdis\/jit603","article-title":"The first identification and retrospective study of Severe Fever with Thrombocytopenia Syndrome in Japan","volume":"209","author":"T Takahashi","year":"2014","journal-title":"J Infect Dis"},{"issue":"5","key":"pntd.0013106.ref005","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.3201\/eid2505.181463","article-title":"Endemic Severe Fever with Thrombocytopenia Syndrome, Vietnam","volume":"25","author":"XC Tran","year":"2019","journal-title":"Emerg Infect Dis"},{"issue":"8","key":"pntd.0013106.ref006","doi-asserted-by":"crossref","first-page":"1878","DOI":"10.3201\/eid2608.200135","article-title":"Genotypic Heterogeneity of Orientia tsutsugamushi in Scrub Typhus Patients and Thrombocytopenia Syndrome Co-infection, Myanmar","volume":"26","author":"AM Win","year":"2020","journal-title":"Emerg Infect Dis"},{"issue":"9","key":"pntd.0013106.ref007","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1056\/NEJMoa1203378","article-title":"A new phlebovirus associated with severe febrile illness in Missouri","volume":"367","author":"LK McMullan","year":"2012","journal-title":"N Engl J Med"},{"key":"pntd.0013106.ref008","unstructured":"Annual review of diseases prioritized under the Research and Development Blueprint (WHO Meeting report, World Health Organization, 2018). 2018."},{"issue":"10","key":"pntd.0013106.ref009","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1016\/S1473-3099(18)30293-7","article-title":"Epidemiological and clinical features of laboratory-diagnosed severe fever with thrombocytopenia syndrome in China, 2011-17: a prospective observational study","volume":"18","author":"H Li","year":"2018","journal-title":"Lancet Infect Dis"},{"issue":"8","key":"pntd.0013106.ref010","article-title":"Endothelial activation and dysfunction in severe fever with thrombocytopenia syndrome","volume":"11","author":"X-K Li","year":"2017","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0013106.ref011","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.ijid.2018.05.013","article-title":"Analysis of clinical features and early warning indicators of death from severe fever with thrombocytopenia syndrome","volume":"73","author":"X Xu","year":"2018","journal-title":"Int J Infect Dis"},{"issue":"11","key":"pntd.0013106.ref012","doi-asserted-by":"crossref","DOI":"10.1016\/j.heliyon.2024.e31289","article-title":"Activated partial thromboplastin time predicts mortality in patients with severe fever with thrombocytopenia syndrome: A multicenter study in north China","volume":"10","author":"W Peng","year":"2024","journal-title":"Heliyon"},{"issue":"12","key":"pntd.0013106.ref013","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1007\/s10096-022-04506-4","article-title":"Analysis of risk factors associated with fatal outcome among severe fever with thrombocytopenia syndrome patients from 2015 to 2019 in Shandong, China","volume":"41","author":"L Song","year":"2022","journal-title":"Eur J Clin Microbiol Infect Dis"},{"issue":"12","key":"pntd.0013106.ref014","article-title":"Associations of diabetes, hypertension and obesity with COVID-19 mortality: a systematic review and meta-analysis","volume":"8","author":"C Li","year":"2023","journal-title":"BMJ Glob Health"},{"issue":"9","key":"pntd.0013106.ref015","doi-asserted-by":"crossref","first-page":"3059","DOI":"10.1007\/s00415-021-10406-y","article-title":"Neurological symptoms, manifestations, and complications associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 19 (COVID-19)","volume":"268","author":"BN Harapan","year":"2021","journal-title":"J Neurol"},{"issue":"10","key":"pntd.0013106.ref016","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1097\/CCM.0000000000006367","article-title":"The Association Between Elevated Myocardial Injury-Related Biomarker (TnI) and Increased Mortality in Patients With Severe Fever With Thrombocytopenia Syndrome","volume":"52","author":"B Liang","year":"2024","journal-title":"Crit Care Med"},{"issue":"1","key":"pntd.0013106.ref017","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.jinf.2014.08.001","article-title":"Severe fever with thrombocytopenia syndrome bunyavirus-related human encephalitis","volume":"70","author":"N Cui","year":"2015","journal-title":"J Infect"},{"key":"pntd.0013106.ref018","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.ijid.2018.03.010","article-title":"Dynamic changes in the immunological characteristics of T lymphocytes in surviving patients with severe fever with thrombocytopenia syndrome (SFTS)","volume":"70","author":"M-M Li","year":"2018","journal-title":"Int J Infect Dis"},{"issue":"1","key":"pntd.0013106.ref019","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/s41392-021-00541-3","article-title":"Clinical effect and antiviral mechanism of T-705 in treating severe fever with thrombocytopenia syndrome","volume":"6","author":"H Li","year":"2021","journal-title":"Signal Transduct Target Ther"},{"key":"pntd.0013106.ref020","doi-asserted-by":"crossref","first-page":"103591","DOI":"10.1016\/j.ebiom.2021.103591","article-title":"Clinical efficacy and safety evaluation of favipiravir in treating patients with severe fever with thrombocytopenia syndrome","volume":"72","author":"Y Yuan","year":"2021","journal-title":"EBioMedicine"},{"issue":"5","key":"pntd.0013106.ref021","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1111\/bjh.19364","article-title":"Prolonged coagulation times in severe fever with thrombocytopenia syndrome virus infection, the indicators of heparin-like effect and increased haemorrhagic risk","volume":"204","author":"N Tang","year":"2024","journal-title":"Br J Haematol"},{"issue":"8","key":"pntd.0013106.ref022","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0009666","article-title":"Coagulation abnormalities in Dengue fever infection: A systematic review and meta-analysis","volume":"15","author":"T Adane","year":"2021","journal-title":"PLoS Negl Trop Dis"},{"issue":"1","key":"pntd.0013106.ref023","article-title":"Levels of peripheral blood routine, biochemical and coagulation parameters in patients with hemorrhagic fever with renal syndrome and their relationship with prognosis: an observational cohort study","volume":"24","author":"W-J Chen","year":"2024","journal-title":"BMC Infectious Diseases"},{"issue":"6","key":"pntd.0013106.ref024","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1093\/infdis\/jiad426","article-title":"Kinetics and Prognostic Significance of Laboratory Markers in Patients With Severe Fever With Thrombocytopenia Syndrome: Insight From a Comprehensive Analysis","volume":"229","author":"H Hou","year":"2024","journal-title":"J Infect Dis"},{"issue":"11","key":"pntd.0013106.ref025","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.5858\/arpa.2012-0599-OA","article-title":"Use of an automated coagulation analyzer to perform heparin neutralization with polybrene in blood samples for routine coagulation testing: practical, rapid, and inexpensive","volume":"137","author":"P Tientadakul","year":"2013","journal-title":"Arch Pathol Lab Med"},{"key":"pntd.0013106.ref026","doi-asserted-by":"crossref","first-page":"725642","DOI":"10.3389\/fcimb.2022.725642","article-title":"The AST\/ALT Ratio (De Ritis Ratio) Represents an Unfavorable Prognosis in Patients in Early-Stage SFTS: An Observational Cohort Study","volume":"12","author":"L Wang","year":"2022","journal-title":"Front Cell Infect Microbiol"},{"issue":"9","key":"pntd.0013106.ref027","article-title":"A scoring model for predicting prognosis of patients with severe fever with thrombocytopenia syndrome","volume":"11","author":"B Jia","year":"2017","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0013106.ref028"},{"issue":"5","key":"pntd.0013106.ref029","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1016\/j.ttbdis.2019.05.008","article-title":"An evaluation of the different biomarkers to discriminate bleeding in Crimean-Congo Hemorrhagic Fever","volume":"10","author":"SA B\u00fcy\u00fcktuna","year":"2019","journal-title":"Ticks Tick Borne Dis"},{"issue":"11","key":"pntd.0013106.ref030","first-page":"1667","article-title":"Early indicators of severity and construction of a risk model for prognosis based upon laboratory parameters in patients with hemorrhagic fever with renal syndrome","volume":"52","author":"H Du","year":"2014","journal-title":"Clin Chem Lab Med"},{"issue":"10","key":"pntd.0013106.ref031","doi-asserted-by":"crossref","DOI":"10.1136\/bcr-2020-235447","article-title":"Why does activated partial thromboplastin time prolongation occur in severe fever with thrombocytopenia syndrome?","volume":"13","author":"A Mizoe","year":"2020","journal-title":"BMJ Case Rep"},{"issue":"4","key":"pntd.0013106.ref032","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1093\/cid\/cir804","article-title":"Hemorrhagic fever caused by a novel Bunyavirus in China: pathogenesis and correlates of fatal outcome","volume":"54","author":"Y-Z Zhang","year":"2012","journal-title":"Clin Infect Dis"}],"updated-by":[{"DOI":"10.1371\/journal.pntd.0013106","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T00:00:00Z","timestamp":1749081600000}}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0013106","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T17:59:57Z","timestamp":1749146397000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0013106"}},"subtitle":[],"editor":[{"given":"Elvina","family":"Viennet","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,5,22]]},"references-count":32,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,5,22]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0013106","relation":{},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,22]]}}}