{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,1,4]],"date-time":"2025-01-04T05:36:27Z","timestamp":1735968987661,"version":"3.32.0"},"reference-count":26,"publisher":"Georg Thieme Verlag KG","issue":"01","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>\n            Introduction\u2003Prethrombin-1 is a Gla-domain lacking enzymatically inactive split product that results from the cleavage of fragment 1 from prothrombin by thrombin in a feedback reaction.<\/jats:p><jats:p>\n            Methods\u2003A prethrombin-1 preparation derived from human plasma was tested for its hemostatic and thrombogenic properties. Animal models of nail clipping (for rabbits) and tail clipping (for mice) were developed to measure blood loss in FVIII-inhibitor or rivaroxaban anticoagulated rabbits and mice, respectively. A modified Wessler test was used in rabbits to assess the thrombogenic potential by Wessler score and clot weight. Studies were performed in groups of three to six for prethrombin-1 dose escalation and comparison with prothrombin, Beriplex\u00ae, FEIBA\u00ae, and saline as a control. Data were analyzed using t-statistics or the Mann Whitney U test as applicable.<\/jats:p><jats:p>\n            Results\u2003Prethrombin-1 has excellent hemostatic properties in anticoagulated mouse and rabbit bleeding models. Wessler tests suggest that in contrast to activated and nonactivated prothrombin complexes, prethrombin-1 has negligible thrombogenic potential.<\/jats:p><jats:p>\n            Conclusion\u2003The thrombin zymogen prethrombin-1 promotes hemostasis with reduced risk of thrombosis. Prethrombin-1 may have potential to become a life-saving treatment for patients who bleed or are at risk of bleeding.<\/jats:p>","DOI":"10.1055\/s-0044-1787720","type":"journal-article","created":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T22:55:31Z","timestamp":1718232931000},"page":"036-045","source":"Crossref","is-referenced-by-count":0,"title":["Prethrombin-1 as a Drug Substance Promoting Hemostasis with Reduced Risk of Thrombosis"],"prefix":"10.1055","volume":"125","author":[{"given":"Johann Georg","family":"Graus","sequence":"additional","affiliation":[{"name":"Biomedizinische Forschung and Bio-Produkte AG, Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Pr\u00fcckler","sequence":"additional","affiliation":[{"name":"Center for Biomedical Research and Translational Surgery, Medical University of Vienna, Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helga","family":"Bergmeister","sequence":"additional","affiliation":[{"name":"Center for Biomedical Research and Translational Surgery, Medical University of Vienna, Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Mader","sequence":"additional","affiliation":[{"name":"Biomedizinische Forschung and Bio-Produkte AG, Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandru","family":"Trefilov","sequence":"additional","affiliation":[{"name":"Biomedizinische Forschung and Bio-Produkte AG, Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"G\u00f6lles","sequence":"additional","affiliation":[{"name":"Biomedizinische Forschung and Bio-Produkte AG, Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianne","family":"Kunschak","sequence":"additional","affiliation":[{"name":"Biomedizinische Forschung and Bio-Produkte AG, Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang","family":"Schramm","sequence":"additional","affiliation":[{"name":"Ludwig-Maximilians University (LMU), Department of Transfusion Medicine and Haemostaseology, Rudolf Marx Stiftung Munich, M\u00fcnchen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2024,6,12]]},"reference":[{"issue":"23","key":"ref1","doi-asserted-by":"crossref","first-page":"8897","DOI":"10.1016\/S0021-9258(19)40670-4","article-title":"Human prothrombin activation","volume":"250","author":"M R Downing","year":"1975","journal-title":"J Biol Chem"},{"issue":"09","key":"ref2","doi-asserted-by":"crossref","first-page":"5386","DOI":"10.1016\/S0021-9258(20)81901-2","article-title":"The kinetics and cofactor dependence of the two cleavages involved in prothrombin activation","volume":"258","author":"M E Nesheim","year":"1983","journal-title":"J Biol Chem"},{"issue":"08","key":"ref3","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1161\/ATVBAHA.107.141911","article-title":"Role of the extrinsic pathway of blood coagulation in hemostasis and thrombosis","volume":"27","author":"N Mackman","year":"2007","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"03","key":"ref4","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1615\/CritRevEukarGeneExpr.v7.i3.40","article-title":"The regulation of clotting factors","volume":"7","author":"M Kalafatis","year":"1997","journal-title":"Crit Rev Eukaryot Gene Expr"},{"issue":"05","key":"ref5","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1182\/blood-2010-09-311035","article-title":"Prothrombin activation on the activated platelet surface optimizes expression of procoagulant activity","volume":"117","author":"J P Wood","year":"2011","journal-title":"Blood"},{"issue":"46","key":"ref6","doi-asserted-by":"crossref","first-page":"38647","DOI":"10.1074\/jbc.M112.407791","article-title":"Prothrombin activation by platelet-associated prothrombinase proceeds through the prethrombin-2 pathway via a concerted mechanism","volume":"287","author":"L M Haynes","year":"2012","journal-title":"J Biol Chem"},{"issue":"10","key":"ref7","first-page":"3642","article-title":"The activation of prothrombin. 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