{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:51:26Z","timestamp":1790315486731,"version":"4.1.0"},"reference-count":46,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T00:00:00Z","timestamp":1646784000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["PG\/15\/82\/31721"],"award-info":[{"award-number":["PG\/15\/82\/31721"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["PG\/20\/17\/35050"],"award-info":[{"award-number":["PG\/20\/17\/35050"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Tenovus Scotland Grampian","award":["G17.03"],"award-info":[{"award-number":["G17.03"]}]},{"name":"Friends of Anchor","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Loss of fibrinogen is a feature of trauma-induced coagulopathy (TIC), and restoring this clotting factor is protective against hemorrhages. We compared the efficacy of cryoprecipitate, and of the fibrinogen concentrates RiaSTAP\u00ae and FibCLOT\u00ae in restoring the clot integrity in models of TIC. Cryoprecipitate and FibCLOT\u00ae produced clots with higher maximal absorbance and enhanced resistance to lysis relative to RiaSTAP\u00ae. The fibrin structure of clots, comprising cryoprecipitate and FibCLOT\u00ae, mirrored those of normal plasma, whereas those with RiaSTAP\u00ae showed stunted fibers and reduced porosity. The hemodilution of whole blood reduced the maximum clot firmness (MCF) as assessed by thromboelastography. MCF could be restored with the inclusion of 1 mg\/mL of fibrinogen, but only FibCLOT\u00ae was effective at stabilizing against lysis. The overall clot strength, measured using the Quantra\u00ae hemostasis analyzer, was restored with both fibrinogen concentrates but not cryoprecipitate. \u03b12antiplasmin and plasminogen activator inhibitor-1 (PAI-1) were constituents of cryoprecipitate but were negligible in RiaSTAP\u00ae and FibCLOT\u00ae. Interestingly, cryoprecipitate and FibCLOT\u00ae contained significantly higher factor XIII (FXIII) levels, approximately three-fold higher than RiaSTAP\u00ae. Our data show that 1 mg\/mL fibrinogen, a clinically achievable concentration, can restore adequate clot integrity. However, FibCLOT\u00ae, which contained more FXIII, was superior in normalizing the clot structure and in stabilizing hemodiluted clots against mechanical and fibrinolytic degradation.<\/jats:p>","DOI":"10.3390\/ijms23062944","type":"journal-article","created":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T11:30:38Z","timestamp":1646825438000},"page":"2944","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["The Efficacy of Fibrinogen Concentrates in Relation to Cryoprecipitate in Restoring Clot Integrity and Stability against Lysis"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8127-6102","authenticated-orcid":false,"given":"Claire S.","family":"Whyte","sequence":"first","affiliation":[{"name":"Aberdeen Cardiovascular and Diabetes Centre, Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akriti","family":"Rastogi","sequence":"additional","affiliation":[{"name":"Aberdeen Cardiovascular and Diabetes Centre, Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellis","family":"Ferguson","sequence":"additional","affiliation":[{"name":"Aberdeen Cardiovascular and Diabetes Centre, Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Donnarumma","sequence":"additional","affiliation":[{"name":"Aberdeen Cardiovascular and Diabetes Centre, Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7452-0813","authenticated-orcid":false,"given":"Nicola J.","family":"Mutch","sequence":"additional","affiliation":[{"name":"Aberdeen Cardiovascular and Diabetes Centre, Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/s41572-021-00264-3","article-title":"Trauma-induced coagulopathy","volume":"7","author":"Simmons","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1097\/TA.0000000000000729","article-title":"Mechanisms of early trauma-induced coagulopathy: The clot thickens or not?","volume":"79","author":"Dobson","year":"2015","journal-title":"J. Trauma Acute Care Surg."},{"key":"ref_3","first-page":"23","article-title":"Fibrinogen replacement therapy: A critical review of the literature","volume":"10","author":"Franchini","year":"2012","journal-title":"High. Speed Blood Transfus. Equip."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"29","DOI":"10.5482\/HAMO-13-07-0038","article-title":"The role of fibrinogen in trauma-induced coagulopathy","volume":"34","author":"Schlimp","year":"2014","journal-title":"H\u00e4mostaseologie"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1097\/TA.0b013e3181a602a7","article-title":"Coagulopathy by hypothermia and acidosis: Mechanisms of thrombin generation and fibrinogen availability","volume":"67","author":"Martini","year":"2009","journal-title":"J. Trauma Acute Care Surg."},{"key":"ref_6","first-page":"360","article-title":"Hemostatic factors and replacement of major blood loss with plasma-poor red cell concentrates","volume":"81","author":"Hiippala","year":"1995","journal-title":"Anesth. Analg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1097\/SHK.0000000000000088","article-title":"An update on the coagulopathy of trauma","volume":"41","author":"Maegele","year":"2014","journal-title":"Shock"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1160\/TH04-12-0799","article-title":"Relationship between factor XIII activity, fibrinogen, haemostasis screening tests and postoperative bleeding in cardiopulmonary bypass surgery","volume":"93","author":"Blome","year":"2005","journal-title":"Thromb. Haemost."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1161\/01.STR.0000017219.83330.FF","article-title":"Increased risk for postoperative hemorrhage after intracranial surgery in patients with decreased factor XIII activity: Implications of a prospective study","volume":"33","author":"Gerlach","year":"2002","journal-title":"Stroke"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1055\/s-0036-1585079","article-title":"Perioperative coagulation management in a patient with congenital afibrinogenemia during revision total hip arthroplasty","volume":"42","author":"Kubisz","year":"2016","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1111\/j.1538-7836.2012.04752.x","article-title":"Fibrinogen levels during trauma hemorrhage, response to replacement therapy, and association with patient outcomes","volume":"10","author":"Rourke","year":"2012","journal-title":"J. Thromb. Haemost."},{"key":"ref_12","unstructured":"Joint United Kingdom (UK) Blood Transfusion and Tissue Transplantation Services Professional Advisory Committee (2013). 7.3: Transfusion Management of Major Haemorrhage, TSO. [5th ed.]."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/s13054-019-2347-3","article-title":"The European guideline on management of major bleeding and coagulopathy following trauma: Fifth edition","volume":"23","author":"Spahn","year":"2019","journal-title":"Crit. Care"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1093\/bja\/aev134","article-title":"Early cryoprecipitate for major haemorrhage in trauma: A randomised controlled feasibility trial","volume":"115","author":"Curry","year":"2015","journal-title":"Br. J. Anaesth."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.bja.2018.10.055","article-title":"Coagulopathy, cryoprecipitate and CRYOSTAT-2: Realising the potential of a nationwide trauma system for a national clinical trial","volume":"122","author":"Marsden","year":"2019","journal-title":"Br. J. Anaesth."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Simurda, T., Asselta, R., Zolkova, J., Brunclikova, M., Dobrotova, M., Kolkova, Z., Loderer, D., Skornova, I., Hudecek, J., and Lasabova, Z. (2021). Congenital afibrinogenemia and hypofibrinogenemia: Laboratory and genetic testing in rare bleeding disorders with life-threatening clinical manifestations and challenging management. Diagnostics, 11.","DOI":"10.3390\/diagnostics11112140"},{"key":"ref_17","first-page":"32","article-title":"Fibrinogen early in severe trauma studY (FEISTY): Results from an Australian multicentre randomised controlled pilot trial","volume":"23","author":"Winearls","year":"2021","journal-title":"Crit. Care Resusc."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1093\/bja\/aew343","article-title":"Fibrinogen in the initial resuscitation of severe trauma (FiiRST): A randomized feasibility trial","volume":"117","author":"Nascimento","year":"2016","journal-title":"Br. J. Anaesth."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1186\/s13054-018-2086-x","article-title":"Early fibrinogen concentrate therapy for major haemorrhage in trauma (E-FIT 1): Results from a UK multi-centre, randomised, double blind, placebo-controlled pilot trial","volume":"22","author":"Curry","year":"2018","journal-title":"Crit. Care"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1111\/hae.13876","article-title":"Fibrinogen concentrates in hereditary fibrinogen disorders: Past, present and future","volume":"26","author":"Casini","year":"2020","journal-title":"Haemophilia"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1097\/MBC.0000000000000392","article-title":"Yes or no for secondary prophylaxis in afibrinogenemia?","volume":"26","author":"Simurda","year":"2015","journal-title":"Blood Coagul. Fibrinolysis"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4854","DOI":"10.1182\/blood-2007-08-105247","article-title":"Dynamic imaging of fibrin network formation correlated with other measures of polymerization","volume":"111","author":"Chernysh","year":"2008","journal-title":"Blood"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Morrow, G., Carlier, M., Dasgupta, S., Craigen, F., Mutch, N., and Curry, N. (2021). Fibrinogen replacement therapy for traumatic coagulopathy: Does the fibrinogen source matter?. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22042185"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"24259","DOI":"10.1016\/S0021-9258(18)35759-4","article-title":"The effect of fibrin structure on fibrinolysis","volume":"267","author":"Gabriel","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1182\/blood-2010-06-290338","article-title":"The interplay between tissue plasminogen activator domains and fibrin structures in the regulation of fibrinolysis: Kinetic and microscopic studies","volume":"117","author":"Longstaff","year":"2011","journal-title":"Blood"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1161\/01.ATV.20.5.1354","article-title":"Influence of fibrin network conformation and fibrin fiber diameter on fibrinolysis speed: Dynamic and structural approaches by confocal microscopy","volume":"20","author":"Collet","year":"2000","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.bpj.2019.10.034","article-title":"Aggregates dramatically alter fibrin ultrastructure","volume":"118","author":"Seyve","year":"2020","journal-title":"Biophys. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.thromres.2021.06.020","article-title":"Differences in the biochemical composition of three plasma derived human fibrinogen concentrates","volume":"205","author":"Hegener","year":"2021","journal-title":"Thromb. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2389","DOI":"10.1021\/bi00382a046","article-title":"Albumin modulates lateral assembly of fibrin polymers: Evidence of enhanced fine fibril formation and of unique synergism with fibrinogen","volume":"26","author":"Galanakis","year":"1987","journal-title":"Biochemistry"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.thromres.2020.01.001","article-title":"Fibrin clot formation under diverse clotting conditions: Comparing turbidimetry and thromboelastography","volume":"187","author":"Zeng","year":"2020","journal-title":"Thromb. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.actbio.2010.09.007","article-title":"Supplementation of fibrin gels with sodium chloride enhances physical properties and ensuing osteogenic response","volume":"7","author":"Davis","year":"2011","journal-title":"Acta Biomater."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1016\/S0006-3495(98)77638-6","article-title":"Cl- regulates the structure of the fibrin clot","volume":"75","author":"Nagaswami","year":"1998","journal-title":"Biophys. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1111\/j.1538-7836.2009.03633.x","article-title":"For the fibrinogen concentrate study group pharmacokinetics and safety of fibrinogen concentrate","volume":"7","author":"DiMichele","year":"2009","journal-title":"J. Thromb. Haemost."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1111\/jth.14392","article-title":"Clinical pharmacology, efficacy and safety study of a triple-secured fibrinogen concentrate in adults and adolescent patients with congenital fibrinogen deficiency","volume":"17","author":"Lambert","year":"2019","journal-title":"J. Thromb. Haemost."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"10448","DOI":"10.1021\/bi9606206","article-title":"Plasma factor XIII binds specifically to fibrinogen molecules containing gamma chains","volume":"35","author":"Siebenlist","year":"1996","journal-title":"Biochemistry"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"9133","DOI":"10.1073\/pnas.0504120102","article-title":"The elasticity of an individual fibrin fiber in a clot","volume":"102","author":"Collet","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2827","DOI":"10.1016\/S0006-3495(99)77114-6","article-title":"Influence of a natural and a synthetic inhibitor of factor XIIIa on fibrin clot rheology","volume":"77","author":"Ryan","year":"1999","journal-title":"Biophys. J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1182\/blood-2007-01-066837","article-title":"Functional analysis of fibrin \u03b3-chain cross-linking by activated factor XIII: Determination of a cross-linking pattern that maximizes clot stiffness","volume":"110","author":"Standeven","year":"2007","journal-title":"Blood"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1111\/jth.12455","article-title":"The effect of blood coagulation factor XIII on fibrin clot structure and fibrinolysis","volume":"12","author":"Hethershaw","year":"2014","journal-title":"J. Thromb. Haemost."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/0049-3848(79)90027-6","article-title":"Fibrin crosslinks and lysis rates","volume":"14","author":"Gaffney","year":"1979","journal-title":"Thromb. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1172\/JCI110479","article-title":"Significance of cross-linking of \u03b12-plasmin inhibitor to fibrin in inhibition of fibrinolysis and in hemostasis","volume":"69","author":"Sakata","year":"1982","journal-title":"J. Clin. Investig."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6371","DOI":"10.1182\/blood-2011-02-333203","article-title":"The antifibrinolytic function of factor XIII is exclusively expressed through alpha-antiplasmin cross-linking","volume":"117","author":"Fraser","year":"2011","journal-title":"Blood"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1111\/j.1538-7836.2010.03963.x","article-title":"Model thrombi formed under flow reveal the role of factor XIII-mediated cross-linking in resistance to fibrinolysis","volume":"8","author":"Mutch","year":"2010","journal-title":"J. Thromb. Haemost."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2000","DOI":"10.1046\/j.1538-7836.2003.00383.x","article-title":"Thrombus lysis by uPA, scuPA and tPA is regulated by plasma TAFI","volume":"1","author":"Mutch","year":"2003","journal-title":"J. Thromb. Haemost."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1097\/TA.0000000000001282","article-title":"Model of trauma-induced coagulopathy including hemodilution, fibrinolysis, acidosis, and hypothermia","volume":"82","author":"Shenkman","year":"2017","journal-title":"J. Trauma Acute Care Surg."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1111\/jth.13656","article-title":"Development of Shiny app tools to simplify and standardize the analysis of hemostasis assay data: Communication from the SSC of the ISTH","volume":"15","author":"Longstaff","year":"2017","journal-title":"J. Thromb. Haemost."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/6\/2944\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:33:33Z","timestamp":1760135613000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/6\/2944"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,9]]},"references-count":46,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["ijms23062944"],"URL":"https:\/\/doi.org\/10.3390\/ijms23062944","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,9]]}}}