{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T16:38:01Z","timestamp":1782923881753,"version":"3.54.5"},"reference-count":37,"publisher":"Georg Thieme Verlag KG","issue":"12","funder":[{"name":"JSPS KAKENHI","award":["22H03172"],"award-info":[{"award-number":["22H03172"]}]},{"name":"JSPS KAKENHI","award":["22K08153"],"award-info":[{"award-number":["22K08153"]}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["21ek0210154h0002"],"award-info":[{"award-number":["21ek0210154h0002"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["P20-GM152326"],"award-info":[{"award-number":["P20-GM152326"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["T32-GM008315"],"award-info":[{"award-number":["T32-GM008315"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"National Heart Lung and Blood Institute","doi-asserted-by":"crossref","award":["K08-HL171936"],"award-info":[{"award-number":["K08-HL171936"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>To evaluate residual fibrinolysis resistance activity (FRA) in plasma, a detergent-modified plasma clot lysis assay time (dPCLT) was established in which \u03b12-antiplasmin (A2AP) and plasminogen activator inhibitor type 1 (PAI-1) are inactivated without impacting protease activity. We applied this novel assay to severely injured trauma patients\u2019 plasma.<\/jats:p>\n                  <jats:p>Tissue-type plasminogen activator (tPA)-induced plasma clot lysis assays were conducted after detergents- (dPCLT) or vehicle- (sPCLT) treatment, and time to 50% clot lysis was measured (\u201ctransition midpoint\u201d, T m). Residual FRA was then calculated as ([sPCLT T m] - [dPCLT T m]\/[sPCLT T m]) x100% = \u0394 Tm PCLT (%). Assay results were compared to rapid thromboelastography (TEG) LY30, tPA TEG LY30, and plasma fibrinolysis biomarkers in polytrauma patients\u2019 plasma (N=43).<\/jats:p>\n                  <jats:p>\u0394 Tm PCLT(%) in normal plasma (N=5) was 63.0\u2009\u00b1\u20098.3 whereas in A2AP-depleted plasma was -19.1\u2009\u00b1\u20091.3%, Plasmin-antiplasmin (PAP) complex increased after complete lysis of sPCLT, whereas that in dPCLT was negligible in normal plasma. In trauma plasma, significant correlations between \u0394 Tm PCLT and active PAI-1 (r = 0.85, p&lt;0.0001), PAP complex (r = -0.85, p&lt;0.0001), free A2AP (r = 0.66, p&lt;0.0001), total A2AP levels (r = 0.52, p=0.001) and tPA TEG LY30 (r = -0.85, p&lt;0.0001) were found. dPCLT in hyperfibrinolysis patients diagnosed by tPA TEG was significantly shorter than those with low fibrinolysis [10.2 \u00b1\u20096.4 minutes versus 20.2 \u00b1\u20092.1 minutes, p=0.0006].<\/jats:p>\n                  <jats:p>Hyperfibrinolysis after trauma is significantly related to exhaustion of FRA, and our novel assay appears to quickly assess this state and may be a useful clinical diagnostic after additional validation.<\/jats:p>","DOI":"10.1055\/a-2508-3424","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T19:23:48Z","timestamp":1737487428000},"page":"1205-1215","source":"Crossref","is-referenced-by-count":5,"title":["A Novel Fibrinolysis Resistance Capacity Assay can Detect Fibrinolytic Phenotypes in Trauma Patients"],"prefix":"10.1055","volume":"125","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9720-8155","authenticated-orcid":false,"given":"Christopher D.","family":"Barrett","sequence":"additional","affiliation":[{"name":"Division of Acute Care Surgery, Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska, United States"},{"name":"Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4833-8580","authenticated-orcid":false,"given":"Yuko","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Hamamatsu University School of Medicine, Hamamatsu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernest E.","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of Surgery, Ernest E Moore Shock Trauma Center at Denver Health, Denver, Colorado, United States"},{"name":"Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5939-3828","authenticated-orcid":false,"given":"Hunter B.","family":"Moore","sequence":"additional","affiliation":[{"name":"Division of Solid Organ Transplantation, Department of Surgery, AdventHealth Porter, Denver, Colorado, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth R.","family":"Maginot","sequence":"additional","affiliation":[{"name":"Division of Acute Care Surgery, Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Collin M.","family":"White","sequence":"additional","affiliation":[{"name":"Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Halima","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"Division of Acute Care Surgery, Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flobater I.","family":"Gawargi","sequence":"additional","affiliation":[{"name":"Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James G.","family":"Chandler","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Sauaia","sequence":"additional","affiliation":[{"name":"Sauaia Statistical Solutions, LLC, Denver, Colorado, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7398-9732","authenticated-orcid":false,"given":"Tetsumei","family":"Urano","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Hamamatsu University School of Medicine, Hamamatsu, Japan"},{"name":"Department of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2025,1,21]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1093\/oxfordjournals.bmb.a070327","article-title":"Fibrinolysis and intrinsic haemostasis","volume":"20","author":"J L Stafford","year":"1964","journal-title":"Br Med Bull"},{"issue":"03","key":"ref2","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1111\/j.1365-2141.2005.05444.x","article-title":"Molecular 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plasminogen-binding sites","volume":"286","author":"J H Foley","year":"2011","journal-title":"J Biol Chem"},{"issue":"01","key":"ref6","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1097\/XCS.0000000000001027","article-title":"Differentiating pathologic from physiologic fibrinolysis: not as simple as conventional thrombelastography","volume":"239","author":"H B Moore","year":"2024","journal-title":"J Am Coll Surg"},{"issue":"04","key":"ref7","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.jamcollsurg.2016.01.006","article-title":"Acute fibrinolysis shutdown after injury occurs frequently and increases mortality: a multicenter evaluation of 2,540 severely injured patients","volume":"222","author":"H B Moore","year":"2016","journal-title":"J Am Coll Surg"},{"issue":"01","key":"ref8","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.jamcollsurg.2017.02.018","article-title":"Viscoelastic tissue plasminogen activator challenge predicts massive 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Conversions between different forms by sodium dodecyl sulphate","volume":"209","author":"T Urano","year":"1992","journal-title":"Eur J Biochem"},{"issue":"06","key":"ref25","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/0049-3848(93)90053-Q","article-title":"Dissociation of alpha 2-plasmin-inhibitor-plasmin complex and regeneration of plasmin activity by SDS treatment","volume":"69","author":"D Yan","year":"1993","journal-title":"Thromb Res"},{"issue":"05","key":"ref26","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1016\/j.jamcollsurg.2015.01.026","article-title":"Plasma is the physiologic buffer of tissue plasminogen activator-mediated fibrinolysis: rationale for plasma-first resuscitation after life-threatening hemorrhage","volume":"220","author":"H B Moore","year":"2015","journal-title":"J Am Coll Surg"},{"issue":"01","key":"ref27","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1097\/SHK.0000000000000245","article-title":"Hemolysis exacerbates hyperfibrinolysis, whereas platelolysis shuts down fibrinolysis: evolving concepts of the spectrum of fibrinolysis in response to severe injury","volume":"43","author":"H B Moore","year":"2015","journal-title":"Shock"},{"issue":"13","key":"ref28","doi-asserted-by":"crossref","first-page":"2969","DOI":"10.1002\/j.1460-2075.1995.tb07299.x","article-title":"Molecular evolution of plasminogen activator inhibitor-1 functional stability","volume":"14","author":"M B Berkenpas","year":"1995","journal-title":"EMBO J"},{"issue":"06","key":"ref29","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1097\/TA.0000000000001685","article-title":"Human neutrophil elastase mediates fibrinolysis shutdown through competitive degradation of plasminogen and generation of angiostatin","volume":"83","author":"C D Barrett","year":"2017","journal-title":"J Trauma Acute Care Surg"},{"issue":"04","key":"ref30","doi-asserted-by":"crossref","first-page":"102463","DOI":"10.1016\/j.rpth.2024.102463","article-title":"Evaluation of thrombomodulin\/thrombin activatable fibrinolysis inhibitor function in plasma using tissue-type plasminogen activator-induced plasma clot lysis time","volume":"8","author":"T Urano","year":"2024","journal-title":"Res Pract Thromb Haemost"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1136\/jcp.s3-4.1.110","article-title":"The significance of coagulative and thrombotic changes after haemorrhage and injury","volume":"4","author":"R M Hardaway","year":"1970","journal-title":"J Clin Pathol Suppl (R Coll Pathol)"},{"issue":"02","key":"ref32","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1056\/NEJMoa2215457","article-title":"Prehospital tranexamic acid for severe trauma","volume":"389","author":"R L Gruen","year":"2023","journal-title":"N Engl J Med"},{"issue":"S 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