{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T06:00:43Z","timestamp":1785477643329,"version":"3.56.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"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:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>International Society on Thrombosis and Haemostasis (ISTH) overt disseminated intravascular coagulation (DIC) scoring is a standard bedside framework for infection-associated coagulopathy but does not capture anticoagulant-pathway markers. The study examined whether admission antithrombin III (AT-III) activity provided risk-enrichment information for septic shock among adults admitted with infection below the ISTH 2001 overt-DIC threshold.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The study retrospectively analyzed 1,286 adults admitted with infection. AT-III activity was evaluated in the ISTH-complete and below-threshold subsets and compared with ISTH 2001 and 2025 SSC overt-DIC scores. Retrospective temporal adjudication compared first valid AT-III report availability with operational septic-shock onset. In a clinically indicated lactate-measured subset, the study assessed whether AT-III added discrimination beyond age, sex, and lactate. Firth-penalized regression evaluated the conditional association of AT-III with septic shock beyond age, sex, and raw ISTH components.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 1,027 ISTH-complete patients, 974 (94.8%) were below the ISTH 2001 overt-DIC threshold, including 44 of 60 septic-shock cases. In this subgroup, 43 of 44 shock cases had AT-III activity &amp;lt;80%; the area under the curve (AUC) was 0.844 and the positive predictive value was 9.37% (43\/459). Of 82 septic-shock admissions, 74 were temporally adjudicable: 62 were incident and 12 were prevalent or concurrent at AT-III report availability. In incident cases, AT-III report availability preceded operational shock onset by a median of 7.6\u202fh (interquartile range (IQR) 5.0\u20139.6); sampling therefore also preceded onset. In the lactate-measured subset (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f518), AT-III increased AUC beyond age, sex, and lactate from 0.740 to 0.821; this increment persisted in the incident-shock analysis (0.680\u20130.792). In the primary Firth model, lower AT-III activity remained conditionally associated with shock (OR 3.10 per 1-SD decrease); the apparent and bootstrap-corrected AUCs were 0.900 and 0.888.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Admission AT-III activity was associated with septic shock within the large ISTH below-threshold infection subgroup and provided high-sensitivity, low-positive-predictive-value enrichment information. Retrospectively reconstructed temporal ordering demonstrated a report-release-to-operational-onset interval in incident cases but does not establish prospective prediction, prospective workflow performance, or clinical benefit. AT-III should not be used as a standalone trigger for escalation decisions. Prospective, time-stamped validation is required.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1899792","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T05:38:40Z","timestamp":1785476320000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Admission antithrombin III activity as a risk-enrichment marker for septic shock below the ISTH overt-DIC threshold"],"prefix":"10.3389","volume":"13","author":[{"given":"Tao","family":"Zhou","sequence":"first","affiliation":[{"name":"The First Clinical Medical College of Nanjing Medical University","place":["Nanjing, China"]},{"name":"Department of Geriatrics, Jiangsu Provincial Key Laboratory of Geriatrics, The First Affiliated Hospital of Nanjing Medical University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanying","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Hematology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi Medical Center","place":["Wuxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guohua","family":"Jiang","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College of Nanjing Medical University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Jiangsu Provincial Key Laboratory of Geriatrics, The First Affiliated Hospital of Nanjing Medical University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Jiangsu Provincial Key Laboratory of Geriatrics, The First Affiliated Hospital of Nanjing Medical University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Jiangsu Provincial Key Laboratory of Geriatrics, The First Affiliated Hospital of Nanjing Medical University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The third international consensus definitions for Sepsis and septic shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, regional, and national sepsis incidence and mortality, 1990\u20132017: analysis for the global burden of disease study","volume":"395","author":"Rudd","year":"2020","journal-title":"Lancet"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.1007\/s00134-020-06151-x","article-title":"Incidence and mortality of hospital- and ICU-treated sepsis: results from an updated and expanded systematic review and meta-analysis","volume":"46","author":"Fleischmann-Struzek","year":"2020","journal-title":"Intensive Care Med"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1056\/NEJM199908193410807","article-title":"Disseminated intravascular coagulation","volume":"341","author":"Levi","year":"1999","journal-title":"N Engl J Med"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"16037","DOI":"10.1038\/nrdp.2016.37","article-title":"Disseminated intravascular coagulation","volume":"2","author":"Gando","year":"2016","journal-title":"Nat Rev Dis Primers"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1055\/s-0037-1616068","article-title":"Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation","volume":"86","author":"Taylor","year":"2001","journal-title":"Thromb Haemost"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1007\/s00134-021-06506-y","article-title":"Surviving Sepsis campaign: international guidelines for Management of Sepsis and Septic Shock 2021","volume":"47","author":"Evans","year":"2021","journal-title":"Intensive Care Med"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"2356","DOI":"10.1016\/j.jtha.2025.03.038","article-title":"Updated definition and scoring of disseminated intravascular coagulation in 2025: communication from the ISTH SSC subcommittee on disseminated intravascular coagulation","volume":"23","author":"Iba","year":"2025","journal-title":"J Thromb Haemost"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.jtha.2022.10.022","article-title":"Communication from the scientific and standardization Committee of the International Society on thrombosis and Haemostasis on sepsis-induced coagulopathy in the management of sepsis","volume":"21","author":"Iba","year":"2023","journal-title":"J Thromb Haemost"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1160\/TH15-08-0687","article-title":"Antithrombin: anti-inflammatory properties and clinical applications","volume":"115","author":"Levy","year":"2016","journal-title":"Thromb Haemost"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s44158-025-00243-0","article-title":"Protein C in adult patients with sepsis: from pathophysiology to monitoring and supplementation","volume":"5","author":"Coloretti","year":"2025","journal-title":"J Anesth Analg Crit Care"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s13613-025-01434-2","article-title":"Biomarkers of sepsis-induced coagulopathy: diagnostic insights and potential therapeutic implications","volume":"15","author":"Curtiaud","year":"2025","journal-title":"Ann Intensive Care"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1126\/science.3649921","article-title":"Heparin promotes the inactivation of antithrombin by neutrophil elastase","volume":"237","author":"Jordan","year":"1987","journal-title":"Science"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"10493","DOI":"10.1016\/S0021-9258(18)81648-9","article-title":"Inactivation of human antithrombin by neutrophil elastase: kinetics of the heparin-dependent reaction","volume":"264","author":"Jordan","year":"1989","journal-title":"J Biol Chem"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1111\/j.1574-695X.2008.00480.x","article-title":"Neutrophil elastase and syndecan shedding contribute to antithrombin depletion in murine anthrax","volume":"54","author":"Chung","year":"2008","journal-title":"FEMS Immunol Med Microbiol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1177\/10962964251376946","article-title":"High dose of antithrombin suppresses neutrophil extracellular trap formation in human neutrophils in vitro following lipopolysaccharide- and platelet-induced stimulation","volume":"26","author":"Aoyama-Ishikawa","year":"2025","journal-title":"Surg Infect"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.thromres.2019.07.002","article-title":"Significance of plasma fibrinogen level and antithrombin activity in sepsis: a multicenter cohort study using a cubic spline model","volume":"181","author":"Matsubara","year":"2019","journal-title":"Thromb Res"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"10760296241271334","DOI":"10.1177\/10760296241271334","article-title":"Comparison of three different disseminated intravascular coagulation (DIC) criteria and diagnostic and prognostic value of antithrombin investigation in patients with confirmed sepsis-induced coagulopathy (SIC)","volume":"30","author":"Wei","year":"2024","journal-title":"Clin Appl Thromb Hemost"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1645146","DOI":"10.3389\/fmed.2025.1645146","article-title":"The diagnostic and prognostic value of antithrombin III activity for sepsis-induced coagulopathy in septic patients: a prospective observational study","volume":"12","author":"Li","year":"2025","journal-title":"Front Med (Lausanne)"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/s40560-026-00862-x","article-title":"Association between antithrombin levels and prognosis in patients with sepsis: a retrospective cohort study based on the MIMIC-IV and MIMIC-III databases","volume":"14","author":"Ren","year":"2026","journal-title":"J Intensive Care"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1097\/EDE.0b013e3181577654","article-title":"The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies","volume":"18","author":"Von Elm","year":"2007","journal-title":"Epidemiology"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"h5527","DOI":"10.1136\/bmj.h5527","article-title":"STARD 2015: an updated list of essential items for reporting diagnostic accuracy studies","volume":"351","author":"Bossuyt","year":"2015","journal-title":"BMJ"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s41073-016-0007-6","article-title":"Sex and gender equity in research: rationale for the SAGER guidelines and recommended use","volume":"1","author":"Heidari","year":"2016","journal-title":"Res Integr Peer Rev"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1080\/01621459.1927.10502953","article-title":"Probable inference, the law of succession, and statistical inference","volume":"22","author":"Wilson","year":"1927","journal-title":"J Am Stat Assoc"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"837","DOI":"10.2307\/2531595","article-title":"Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach","volume":"44","author":"DeLong","year":"1988","journal-title":"Biometrics"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.1016\/S0895-4356(96)00236-3","article-title":"A simulation study of the number of events per variable in logistic regression analysis","volume":"49","author":"Peduzzi","year":"1996","journal-title":"J Clin Epidemiol"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1016\/S0895-4356(01)00341-9","article-title":"Internal validation of predictive models: efficiency of some procedures for logistic regression analysis","volume":"54","author":"Steyerberg","year":"2001","journal-title":"J Clin Epidemiol"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1111\/j.2517-6161.1996.tb02080.x","article-title":"Regression shrinkage and selection via the lasso","volume":"58","author":"Tibshirani","year":"1996","journal-title":"J R Stat Soc Series B Stat Methodol"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v045.i03","article-title":"Mice: multivariate imputation by chained equations in R","volume":"45","author":"Van Buuren","year":"2011","journal-title":"J Stat Softw"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1002\/sim.2929","article-title":"Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond","volume":"27","author":"Pencina","year":"2008","journal-title":"Stat Med"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1097\/EDE.0000000000000018","article-title":"Net reclassification indices for evaluating risk prediction instruments: a critical review","volume":"25","author":"Kerr","year":"2014","journal-title":"Epidemiology"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1177\/0272989X06295361","article-title":"Decision curve analysis: a novel method for evaluating prediction models","volume":"26","author":"Vickers","year":"2006","journal-title":"Med Decis Mak"},{"key":"ref33","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-19425-7","volume-title":"Regression Modeling Strategies: With Applications to Linear Models, Logistic and Ordinal Regression, and Survival Analysis","author":"Harrell","year":"2015"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1186\/s13054-014-0497-x","article-title":"Efficacy and bleeding risk of antithrombin supplementation in septic disseminated intravascular coagulation: a secondary survey","volume":"18","author":"Iba","year":"2014","journal-title":"Crit Care"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1007\/s00134-016-4225-7","article-title":"Antithrombin III for critically ill patients: a systematic review with meta-analysis and trial sequential analysis","volume":"42","author":"Allingstrup","year":"2016","journal-title":"Intensive Care Med"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"e930","DOI":"10.1002\/ams2.930","article-title":"Efficacy of antithrombin administration for patients with sepsis: a systematic review, meta-analysis, and meta-regression","volume":"11","author":"Tsuchida","year":"2024","journal-title":"Acute Med Surg"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.jcrc.2016.06.008","article-title":"The efficacy and safety of antithrombin and recombinant human thrombomodulin combination therapy in patients with severe sepsis and disseminated intravascular coagulation","volume":"36","author":"Yasuda","year":"2016","journal-title":"J Crit Care"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1186\/s13613-024-01380-5","article-title":"Sepsis-induced coagulopathy (SIC) in the management of sepsis","volume":"14","author":"Iba","year":"2024","journal-title":"Ann Intensive Care"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1899792\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T05:38:41Z","timestamp":1785476321000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1899792\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,31]]},"references-count":38,"alternative-id":["10.3389\/fmed.2026.1899792"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1899792","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,31]]},"article-number":"1899792"}}