{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T15:37:42Z","timestamp":1792597062163,"version":"4.5.0"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T00:00:00Z","timestamp":1698796800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Hemostasis and bleeding are difficult to measure. Thrombin generation assays (TGAs) can measure both procoagulant and anticoagulant contributions to coagulation. TGAs might prove useful for the study of bleeding disorders. There has been much progress in TGA methodology over the past two decades, but its clinical significance is uncertain. We will undertake a scoping review of the literature to synthesize available information on the application of TGAs towards the study of bleeding and hemostasis, TGA methodologies being used and to summarize available literature on associations between TGA parameters, bleeding and hemostatic outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) will be searched in collaboration with an information specialist. Title\/abstract and full-text screening will be carried out independently and in duplicate; eligible study types will include randomized controlled trials, non-randomized studies, systematic reviews, and case series reporting TGA results and bleeding\/hemostatic outcomes among humans. Mapping the information identified will be carried out with results presented using qualitative data analytical techniques.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>This scoping review will use published, publicly available information. Research ethics approval will not be required. We will disseminate our findings using conference presentations, peer-reviewed publications, social media, and engagement with knowledge users. This review will outline knowledge gaps concerning TGAs, better delineate its applicability as a clinically relevant assay for bleeding. and seek to identify ongoing barriers to its widespread adoption in clinical research, and eventually, in the clinical setting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Trail regulations<\/jats:title>\n                    <jats:p>\n                      <jats:bold>Registration ID with Open Science Framework:<\/jats:bold>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/osf.io\/zp4ge\" xlink:type=\"simple\">osf.io\/zp4ge<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0293632","type":"journal-article","created":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T13:40:25Z","timestamp":1698846025000},"page":"e0293632","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["Thrombin generation, bleeding and hemostasis in humans: Protocol for a scoping review of the literature"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2405-7912","authenticated-orcid":true,"given":"Joseph R.","family":"Shaw","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler","family":"James","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Douxfils","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yesim","family":"Dargaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3766-4962","authenticated-orcid":true,"given":"Jerrold H.","family":"Levy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herm Jan M.","family":"Brinkman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Risa","family":"Shorr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Siegal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lana A.","family":"Castellucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Gross","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy","family":"Khalife","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Sperling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Page","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3389-2485","authenticated-orcid":true,"given":"Dean","family":"Fergusson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8296-2972","authenticated-orcid":true,"given":"Marc","family":"Carrier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,11,1]]},"reference":[{"key":"pone.0293632.ref001","doi-asserted-by":"crossref","DOI":"10.1002\/9781118833391","volume-title":"Hemostasis and Thrombosis: Practical Guidelines in Clinical Management","author":"HI Saba","year":"2014"},{"issue":"1","key":"pone.0293632.ref002","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1055\/s-0039-1696944","article-title":"Clot Structure and Implications for Bleeding and Thrombosis.","volume":"46","author":"E Mihalko","year":"2020","journal-title":"Semin Thromb Hemost"},{"issue":"8","key":"pone.0293632.ref003","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.1111\/j.1538-7836.2005.01377.x","article-title":"Protease-activated receptors in hemostasis, thrombosis and vascular biology","volume":"3","author":"SR Coughlin","year":"2005","journal-title":"J Thromb Haemost"},{"issue":"5","key":"pone.0293632.ref004","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1111\/j.1365-2141.2005.05612.x","article-title":"The measurement and application of thrombin generation","volume":"130","author":"T. 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Large external quality assessment survey on thrombin generation with CAT: further evidence for the usefulness of normalisation with an external reference plasma","volume":"136","author":"J Perrin","year":"2015","journal-title":"Thromb Res"},{"issue":"5","key":"pone.0293632.ref023","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1111\/jth.15287","article-title":"Recommendations for the measurement of thrombin generation: Communication from the ISTH SSC Subcommittee on Lupus Anticoagulant\/Antiphospholipid Antibodies","volume":"19","author":"M Ninivaggi","year":"2021","journal-title":"J Thromb Haemost"},{"issue":"8","key":"pone.0293632.ref024","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1111\/jth.13743","article-title":"Subcommittee on Factor VIII FcI, and Rare Coagulation Disorders. 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Tripodi","year":"2020","journal-title":"Haematologica"},{"issue":"2","key":"pone.0293632.ref031","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1056\/NEJMra1011170","article-title":"The coagulopathy of chronic liver disease","volume":"365","author":"A Tripodi","year":"2011","journal-title":"N Engl J Med"},{"issue":"6","key":"pone.0293632.ref032","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1055\/s-0040-1715102","article-title":"Thrombin Generation and Cirrhosis: State of the Art and Perspectives.","volume":"46","author":"A Lebreton","year":"2020","journal-title":"Semin Thromb Hemost."},{"issue":"4","key":"pone.0293632.ref033","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1111\/j.1538-7836.2010.03767.x","article-title":"Severe hemophilia with mild bleeding phenotype: molecular characterization and global coagulation profile","volume":"8","author":"E Santagostino","year":"2010","journal-title":"J Thromb 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