{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T03:06:54Z","timestamp":1792206414306,"version":"4.4.0"},"reference-count":26,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2021,2,19]],"date-time":"2021-02-19T00:00:00Z","timestamp":1613692800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013873","name":"Government of Ontario","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013873","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CanVECTOR"},{"name":"CanVECTOR"},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-168987"],"award-info":[{"award-number":["PJT-168987"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-159658"],"award-info":[{"award-number":["PJT-159658"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008360","name":"Hamilton Health Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008360","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009776","name":"McMaster University","doi-asserted-by":"publisher","award":["Internal Career Award"],"award-info":[{"award-number":["Internal Career Award"]}],"id":[{"id":"10.13039\/100009776","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Sepsis is a life-threatening disease characterized by excessive host response to infection that can lead to activation of the coagulation system. Von Willebrand Factor (VWF) and ADAMTS13 are important regulators of hemostasis and their dysregulation during sepsis progression is not well understood. Herein we characterize ADAMTS13 and VWF in septic and non-septic patients. ADAMTS13 activity, ADAMTS13 antigen, VWF antigen, myeloperoxidase, and protein C, were measured in plasma collected from 40 septic patients (20 non-survivors and 20 survivors) and 40 non-septic patients on the first and last day of their ICU stay. ADAMTS13 activity and ADAMTS13 antigen were reduced, whereas VWF antigen was elevated among septic patients compared to non-septic patients and healthy controls. Non-septic patients also exhibited elevated VWF antigen and reduced ADAMTS13 activity, but to a lesser extent than septic patients. Non-survivor septic patients exhibited the lowest levels of ADAMTS13 activity. ADAMTS13 activity:antigen ratio was similar across all patient cohorts suggesting that the specific activity of ADAMTS13 remains unchanged. Therefore, reduced ADAMTS13 function in circulation is likely due to a reduction in circulating levels. We suggest that massive release of VWF in response to inflammation consumes limited circulating ADAMTS13, resulting in the imbalance observed between VWF and ADAMTS13 among septic and to a lesser extent in non-septic ICU patients. Changes to ADAMTS13 did not correlate with myeloperoxidase or protein C levels. Reduced ADAMTS13 activity and antigen, and elevated VWF antigen observed among all patient cohorts on admission remained unchanged in survivors at ICU discharge. Prolonged reduction in ADAMTS13 activity and antigen in septic patients coincides with elevated levels of VWF. The persistent abnormalities in ADAMTS13 and VWF in sepsis patients discharged from the ICU may contribute to a sustained prothrombotic state.<\/jats:p>","DOI":"10.1371\/journal.pone.0247017","type":"journal-article","created":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T02:36:31Z","timestamp":1613788591000},"page":"e0247017","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":36,"title":["Characterization of ADAMTS13 and von Willebrand factor levels in septic and non-septic ICU patients"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3303-5966","authenticated-orcid":true,"given":"Kanwal","family":"Singh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew C.","family":"Kwong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasam","family":"Madarati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharumathy","family":"Kunasekaran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor","family":"Sparring","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison E.","family":"Fox-Robichaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia C.","family":"Liaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin A.","family":"Kretz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,2,19]]},"reference":[{"key":"pone.0247017.ref001","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1182\/blood-2014-05-378638","article-title":"von Willebrand factor, Jedi knight of the bloodstream","volume":"124","author":"TA Springer","year":"2014","journal-title":"Blood"},{"key":"pone.0247017.ref002","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.1182\/blood-2016-04-713289","article-title":"Life in the shadow of a dominant partner: the FVIII-VWF association and its clinical implications for hemophilia A","volume":"128","author":"SW Pipe","year":"2016","journal-title":"Blood"},{"key":"pone.0247017.ref003","doi-asserted-by":"crossref","first-page":"2453","DOI":"10.1111\/trf.14804","article-title":"ADAMTS13: origins, applications, and prospects","volume":"58","author":"WE Plautz","year":"2018","journal-title":"Transfusion"},{"key":"pone.0247017.ref004","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1055\/s-0037-1614408","article-title":"Recovery and half-life of von Willebrand factor-cleaving protease after plasma therapy in patients with thrombotic thrombocytopenic purpura","volume":"81","author":"M Furlan","year":"1999","journal-title":"Thromb. Haemost"},{"key":"pone.0247017.ref005","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1182\/blood-2008-02-078170","article-title":"Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopenic purpura","volume":"112","author":"JE Sadler","year":"2008","journal-title":"Blood"},{"key":"pone.0247017.ref006","doi-asserted-by":"crossref","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":"M Singer","year":"2016","journal-title":"JAMA"},{"key":"pone.0247017.ref007","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1164\/rccm.201504-0781OC","article-title":"Assessment of Global Incidence and Mortality of Hospital-treated Sepsis","volume":"193","author":"C Fleischmann","year":"2016","journal-title":"Am J Respir Crit Care Med"},{"key":"pone.0247017.ref008","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1160\/TH03-03-0182","article-title":"Coagulopathy of sepsis","volume":"91","author":"C. Dempfle","year":"2004","journal-title":"Thromb Haemost"},{"key":"pone.0247017.ref009","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1111\/j.1538-7836.2007.02743.x","article-title":"ADAMTS-13, von Willebrand factor and related parameters in severe sepsis and septic shock","volume":"5","author":"JAK Hovinga","year":"2007","journal-title":"J. Thromb. Haemost"},{"key":"pone.0247017.ref010","doi-asserted-by":"crossref","first-page":"49","DOI":"10.25011\/cim.v40i2.28195","article-title":"Prognostic value of ADAMTS13 in patients with severe sepsis and septic shock","volume":"40","author":"MF Azfar","year":"2017","journal-title":"Clin Invest Med"},{"key":"pone.0247017.ref011","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1007\/s12185-009-0481-4","article-title":"Pivotal role of ADAMTS13 function in liver diseases","volume":"91","author":"M Uemura","year":"2010","journal-title":"Int. J. Hematol"},{"key":"pone.0247017.ref012","doi-asserted-by":"crossref","DOI":"10.3389\/fmed.2017.00232","article-title":"Removal of the C-Terminal Domains of ADAMTS13 by Activated Coagulation Factor XI induces Platelet Adhesion on Endothelial Cells under Flow Conditions","volume":"4","author":"KS Garland","year":"2017","journal-title":"Front. Med"},{"key":"pone.0247017.ref013","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1111\/jth.13953","article-title":"The role of ADAMTS-13 in the coagulopathy of sepsis","volume":"16","author":"M Levi","year":"2018","journal-title":"J. Thromb. Haemost"},{"key":"pone.0247017.ref014","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1111\/j.1538-7836.2009.03313.x","article-title":"von Willebrand factor is a major determinant of ADAMTS-13 decrease during mouse sepsis induced by cecum ligation and puncture","volume":"7","author":"N Lerolle","year":"2009","journal-title":"J Thromb Haemost"},{"key":"pone.0247017.ref015","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1182\/blood-2004-01-0107","article-title":"Effects of inflammatory cytokines on the release and cleavage of the endothelial cell\u2013derived ultralarge von Willebrand factor multimers under flow","volume":"104","author":"A Bernardo","year":"2019","journal-title":"Blood"},{"key":"pone.0247017.ref016","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1160\/TH04-08-0467","article-title":"Changes in ADAMTS13 (von-Willebrand-factor-cleaving protease) activity after induced release of von Willebrand factor during acute systemic inflammation","volume":"93","author":"RA Reiter","year":"2005","journal-title":"Thromb Haemost"},{"key":"pone.0247017.ref017","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1111\/j.1532-5415.2012.03989.x","article-title":"Population burden of long-term survivorship after severe sepsis in Older Americans","volume":"60","author":"TJ Iwashyna","year":"2012","journal-title":"J. Am. Geriatr. Soc"},{"key":"pone.0247017.ref018","first-page":"1","article-title":"Mortality Risk Profiles for Sepsis: A Novel Longitudinal and Multivariable Approach","volume":"30","author":"PC Liaw","year":"2019","journal-title":"Crit. Care Explor"},{"key":"pone.0247017.ref019","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1056\/NEJM200103083441001","article-title":"J. FC. Efficacy and safety of recombinant human activated protein C for severe sepsis","volume":"344","author":"GR Bernard","year":"2001","journal-title":"N. Engl. J. Med"},{"key":"pone.0247017.ref020","first-page":"1","article-title":"International Council for Standardization in Haematology (ICSH) recommendations for laboratory measurement of ADAMTS13","volume":"00","author":"I Mackie","year":"2020","journal-title":"Int. J. Lab. Hematol"},{"key":"pone.0247017.ref021","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1182\/blood-2015-12-688747","article-title":"Human neutrophil peptides inhibit cleavage of von Willebrand factor by ADAMTS13: a potential link of inflammation to TTP","volume":"128","author":"VG Pillai","year":"2016","journal-title":"Blood"},{"key":"pone.0247017.ref022","first-page":"2","article-title":"Sepsis-associated disseminated intravascular coauglation and thromboembolic disease","author":"N Semeraro","year":"2010","journal-title":"Mediterr. J. Hematol. Infect. Dis"},{"key":"pone.0247017.ref023","doi-asserted-by":"crossref","first-page":"R151","DOI":"10.1186\/cc11466","article-title":"Prognostic utility and characterization of cell-free DNA in patients with severe sepsis","volume":"16","author":"DJ Dwivedi","year":"2012","journal-title":"Crit. Care"},{"key":"pone.0247017.ref024","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1182\/blood-2005-03-1087","article-title":"Severe secondary deficiency of von Willebrand factor\u2013cleaving protease (ADAMTS13) in patients with sepsis-induced disseminated intravascular coagulation: its correlation with development of renal failure","volume":"107","author":"T Ono","year":"2006","journal-title":"Blood"},{"key":"pone.0247017.ref025","doi-asserted-by":"crossref","first-page":"121","DOI":"10.3324\/haematol.10262","article-title":"Acquired ADAMTS13 deficiency in pediatric patients with severe sepsis","volume":"92","author":"TC Nguyen","year":"2007","journal-title":"Haematologica"},{"key":"pone.0247017.ref026","first-page":"18","article-title":"Understanding Long-Term Outcomes Following Sepsis: Implications and Challenges","author":"M Shankar-Hari","year":"2016","journal-title":"Curr. Infect. Dis. Rep"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0247017","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T02:36:58Z","timestamp":1613788618000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0247017"}},"subtitle":[],"editor":[{"given":"Pablo","family":"Garcia de Frutos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,2,19]]},"references-count":26,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2,19]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0247017","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,19]]}}}