{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T04:40:20Z","timestamp":1792039220424,"version":"4.4.0"},"reference-count":141,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T00:00:00Z","timestamp":1738713600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The plasma protein fibrinogen is critical for haemostasis and wound healing, serving as the structural foundation of the blood clot. Through a complex interaction between coagulation factors, the soluble plasma fibrinogen is converted to insoluble fibrin networks, which form the skeleton of the blood clot, an essential step to limit blood loss after vascular trauma. This review examines the molecular mechanisms by which fibrinogen modulates bleeding, focusing on its interactions with other proteins that maintain fibrin network stability and prevent premature breakdown. Moreover, we also cover the role of fibrinogen in ensuring clot stability through the physiological interaction with platelets. We address the therapeutic applications of fibrinogen across various clinical contexts, including trauma-induced coagulopathy, postpartum haemorrhage, and cardiac surgery. Importantly, a full understanding of protein function will allow the development of new therapeutics to limit blood loss following vascular trauma, which remains a key cause of mortality worldwide. While current management strategies help with blood loss following vascular injury, they are far from perfect and future research should prioritise refining fibrinogen replacement strategies and developing novel agents to stabilise the fibrin network. Exploiting fibrinogen\u2019s molecular properties holds significant potential for improving outcomes in trauma care, surgical interventions and obstetric haemorrhage.<\/jats:p>","DOI":"10.3390\/ijms26031336","type":"journal-article","created":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T04:15:41Z","timestamp":1738728941000},"page":"1336","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Exploiting the Molecular Properties of Fibrinogen to Control Bleeding Following Vascular Injury"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4129-2074","authenticated-orcid":false,"given":"Tanjot","family":"Singh","sequence":"first","affiliation":[{"name":"Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Woodhouse, Leeds LS2 9JT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Hasan","sequence":"additional","affiliation":[{"name":"St James\u2019s University Hospital, Beckett St, Harehills, Leeds LS9 7TF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thembaninkosi G.","family":"Gaule","sequence":"additional","affiliation":[{"name":"Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Woodhouse, Leeds LS2 9JT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1636-3725","authenticated-orcid":false,"given":"Ramzi A.","family":"Ajjan","sequence":"additional","affiliation":[{"name":"Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Woodhouse, Leeds LS2 9JT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,5]]},"reference":[{"key":"ref_1","unstructured":"Kaur, J., and Jain, A. (2022, January 01). Fibrinogen, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK537184\/#:~:text=%5B9%5D%20The%20minimum%20amount%20of."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Pechlivani, N., Kearney, K.J., and Ajjan, R.A. (2021). Fibrinogen and Antifibrinolytic Proteins: Interactions and Future Therapeutics. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222212537"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"R52","DOI":"10.1186\/cc8943","article-title":"Management of bleeding following major trauma: An updated European guideline","volume":"14","author":"Rossaint","year":"2010","journal-title":"Crit. Care"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2768","DOI":"10.1016\/j.injury.2021.07.040","article-title":"Preventable death in trauma: A systematic review on definition and classification","volume":"52","author":"Hakkenbrak","year":"2021","journal-title":"Injury"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Gaule, T.G., and Ajjan, R.A. (2021). Fibrin(ogen) as a Therapeutic Target: Opportunities and Challenges. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22136916"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1093\/bja\/aeq161","article-title":"Role of fibrinogen in trauma-induced coagulopathy","volume":"105","author":"Fries","year":"2010","journal-title":"BJA Br. J. Anaesth."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1182\/blood-2014-08-552000","article-title":"How I use fibrinogen replacement therapy in acquired bleeding","volume":"125","author":"Levy","year":"2015","journal-title":"Blood"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/j.1749-6632.1983.tb23232.x","article-title":"Covalent Structure of Fibrinogen","volume":"408","author":"Henschen","year":"1983","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1006\/bbrc.1993.1074","article-title":"The Role of Amino-Terminal Disulfide Bonds in the Structure and Assembly of Human Fibrinogen","volume":"190","author":"Huang","year":"1993","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.1111\/j.1538-7836.2005.01365.x","article-title":"Fibrinogen and fibrin structure and functions","volume":"3","author":"Mosesson","year":"2005","journal-title":"J. Thromb. Haemost."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1002\/rth2.12191","article-title":"Fibrinogen and fibrin: An illustrated review","volume":"3","author":"Pieters","year":"2019","journal-title":"Res. Pract. Thromb. Haemost."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3005","DOI":"10.1016\/j.jtha.2023.08.014","article-title":"Fibrinogen and fibrin: Synthesis, structure, and function in health and disease","volume":"21","author":"Wolberg","year":"2023","journal-title":"J. Thromb. Haemost."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"100733","DOI":"10.1016\/j.blre.2020.100733","article-title":"Interplay between platelets and coagulation","volume":"46","author":"Sang","year":"2020","journal-title":"Blood Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.blre.2014.09.003","article-title":"Fibrinolysis and the control of blood coagulation","volume":"29","author":"Chapin","year":"2015","journal-title":"Blood Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e13","DOI":"10.1161\/ATVBAHA.117.308564","article-title":"Fibrinogen and Fibrin in Hemostasis and Thrombosis","volume":"37","author":"Kattula","year":"2017","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/38947","article-title":"Crystal structures of fragment D from human fibrinogen and its crosslinked counterpart from fibrin","volume":"389","author":"Spraggon","year":"1997","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1111\/jth.13280","article-title":"Transport physics and biorheology in the setting of hemostasis and thrombosis","volume":"14","author":"Brass","year":"2016","journal-title":"J. Thromb. Haemost."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1111\/j.1538-7836.2011.04203.x","article-title":"Hindered dissolution of fibrin formed under mechanical stress","volume":"9","author":"Machovich","year":"2011","journal-title":"J. Thromb. Haemost."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1007\/s10856-024-06775-1","article-title":"Flow affects the structural and mechanical properties of the fibrin network in plasma clots","volume":"35","author":"Eyisoylu","year":"2024","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Miszta, A., Huskens, D., Donkervoort, D., Roberts, M.J.M., Wolberg, A.S., and de Laat, B. (2021). Assessing Plasmin Generation in Health and Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052758"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1016\/j.str.2016.08.009","article-title":"Structural Basis of Interfacial Flexibility in Fibrin Oligomers","volume":"24","author":"Zhmurov","year":"2016","journal-title":"Structure"},{"key":"ref_22","first-page":"174","article-title":"The Role of Fibrin(ogen) in Wound Healing and Infection Control","volume":"48","author":"Kearney","year":"2021","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Cialdai, F., Risaliti, C., and Monici, M. (2022). Role of fibroblasts in wound healing and tissue remodeling on Earth and in space. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.958381"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1042\/bj20021234","article-title":"Transglutaminases: Nature\u2019s biological glues","volume":"368","author":"Griffin","year":"2002","journal-title":"Biochem. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1152\/physrev.00016.2010","article-title":"Factor XIII: A Coagulation Factor With Multiple Plasmatic and Cellular Functions","volume":"91","author":"Muszbek","year":"2011","journal-title":"Physiol. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1182\/blood-2012-09-306639","article-title":"Mechanisms of fibrin polymerization and clinical implications","volume":"121","author":"Weisel","year":"2013","journal-title":"Blood"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1002\/rth2.12183","article-title":"Fibrinogen \u03b1C domain: Its importance in physiopathology","volume":"3","author":"Soria","year":"2019","journal-title":"Res. Pract. Thromb. Haemost."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e68761","DOI":"10.7554\/eLife.68761","article-title":"Fibrinogen \u03b1C-subregions critically contribute blood clot fibre growth, mechanical stability, and resistance to fibrinolysis","volume":"10","author":"McPherson","year":"2021","journal-title":"eLife"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1146\/annurev-biophys-111821-072110","article-title":"Nanomechanics of Blood Clot and Thrombus Formation","volume":"51","author":"Domingues","year":"2022","journal-title":"Annu. Rev. Biophys."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1161\/ATVBAHA.122.317164","article-title":"Fibrinogen and Factor XIII in Venous Thrombosis and Thrombus Stability","volume":"42","author":"Wolberg","year":"2022","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1111\/j.1538-7836.2009.03378.x","article-title":"The structure and function of platelet integrins","volume":"7","author":"Bennett","year":"2009","journal-title":"J. Thromb. Haemost."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1097\/00062752-200109000-00002","article-title":"Mechanisms of platelet aggregation","volume":"8","author":"Savage","year":"2001","journal-title":"Curr. Opin. Hematol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Huang, Y., Wang, J., Guo, Y., Shen, L., and Li, Y. (2024). Fibrinogen binding to activated platelets and its biomimetic thrombus-targeted thrombolytic strategies. Int. J. Biol. Macromol., 274.","DOI":"10.1016\/j.ijbiomac.2024.133286"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Gao, D., Sun, C.W., Woodley, A.B., and Dong, J. (2023). Clot Retraction and Its Correlation with the Function of Platelet Integrin \u03b1IIb\u03b23. Biomedicines, 11.","DOI":"10.3390\/biomedicines11092345"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Risman, R.A., Paynter, B., Percoco, V., Shroff, M., Bannish, B.E., and Tutwiler, V. (2024). Internal fibrinolysis of fibrin clots is driven by pore expansion. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-52844-4"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1055\/s-0040-1718923","article-title":"Fibrinolysis in Acute and Chronic Cardiovascular Disease","volume":"47","author":"Kietsiriroje","year":"2021","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"100081","DOI":"10.1016\/j.rpth.2023.100081","article-title":"Fibrinolysis: An illustrated review","volume":"7","author":"Risman","year":"2023","journal-title":"Res. Pract. Thromb. Haemost."},{"key":"ref_38","unstructured":"Jilani, T.N., and Siddiqui, A.H. (2024, September 17). Tissue Plasminogen Activator, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK507917\/."},{"key":"ref_39","unstructured":"Katz, J.M., and Tadi, P. (2024, September 17). Physiology, Plasminogen Activation, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK539745\/."},{"key":"ref_40","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_41","doi-asserted-by":"crossref","unstructured":"Hudson, N.E. (2017). Biophysical Mechanisms Mediating Fibrin Fiber Lysis. BioMed Res. Int., 2017.","DOI":"10.1155\/2017\/2748340"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Sillen, M., and Declerck, P.J. (2021). A Narrative Review on Plasminogen Activator Inhibitor-1 and Its (Patho)Physiological Role: To Target or Not to Target?. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052721"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Singh, S., Saleem, S., and Reed, G.L. (2020). Alpha2-Antiplasmin: The Devil You Don\u2019t Know in Cerebrovascular and Cardiovascular Disease. Front. Cardiovasc. Med., 7.","DOI":"10.3389\/fcvm.2020.608899"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.2174\/1389450120666190715102510","article-title":"Recognition of Plasminogen Activator Inhibitor Type 1 as the Primary Regulator of Fibrinolysis","volume":"20","author":"Urano","year":"2019","journal-title":"Curr. Drug Targets"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Altalhi, R., Pechlivani, N., and Ajjan, R.A. (2021). PAI-1 in Diabetes: Pathophysiology and Role as a Therapeutic Target. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22063170"},{"key":"ref_46","first-page":"096","article-title":"Clot Structure and Implications for Bleeding and Thrombosis","volume":"46","author":"Mihalko","year":"2019","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1111\/jth.15647","article-title":"Alpha-2-macroglobulin in hemostasis and thrombosis: An underestimated old double-edged sword","volume":"20","author":"Lagrange","year":"2022","journal-title":"J. Thromb. Haemost."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Napolitano, F., Giudice, V., Selleri, C., and Montuori, N. (2023). Plasminogen System in the Pathophysiology of Sepsis: Upcoming Biomarkers. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241512376"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/j.transci.2019.08.007","article-title":"Inherited disorders of the fibrinolytic pathway","volume":"58","author":"Jain","year":"2019","journal-title":"Transfus. Apher. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Sillen, M., and Declerck, P.J. (2021). Thrombin Activatable Fibrinolysis Inhibitor (TAFI): An Updated Narrative Review. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073670"},{"key":"ref_51","first-page":"d556-68","article-title":"Thrombin-activatable fibrinolysis inhibitor TAFI deficient mice","volume":"7","author":"Nagashima","year":"2002","journal-title":"Front. Biosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e128379","DOI":"10.1172\/jci.insight.128379","article-title":"TAFI deficiency causes maladaptive vascular remodeling after hemophilic joint bleeding","volume":"4","author":"Wyseure","year":"2019","journal-title":"JCI Insight"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Vandooren, J., and Itoh, Y. (2021). Alpha-2-Macroglobulin in Inflammation, Immunity and Infections. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.803244"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Yaron, J.R., Zhang, L., Guo, Q., Haydel, S.E., and Lucas, A.R. (2021). Fibrinolytic Serine Proteases, Therapeutic Serpins and Inflammation: Fire Dancers and Firestorms. Front. Cardiovasc. Med., 8.","DOI":"10.3389\/fcvm.2021.648947"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Pereira, R.V.S., EzEldeen, M., Ugarte-Berzal, E., Martens, E., Malengier-Devlies, B., Vandooren, J., Vranckx, J.J., Matthys, P., and Opdenakker, G. (2023). Physiological fibrin hydrogel modulates immune cells and molecules and accelerates mouse skin wound healing. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1170153"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Bayer, I.S. (2022). Advances in Fibrin-Based Materials in Wound Repair: A Review. Molecules, 27.","DOI":"10.3390\/molecules27144504"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Tottoli, E.M., Dorati, R., Genta, I., Chiesa, E., Pisani, S., and Conti, B. (2020). Skin Wound Healing Process and New Emerging Technologies for Skin Wound Care and Regeneration. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12080735"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Solarte David, V.A., G\u00fciza-Arg\u00fcello, V.R., Arango-Rodr\u00edguez, M.L., Sossa, C.L., and Becerra-Bayona, S.M. (2022). Decellularized Tissues for Wound Healing: Towards Closing the Gap Between Scaffold Design and Effective Extracellular Matrix Remodeling. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.821852"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1111\/jth.12078","article-title":"The incidence and magnitude of fibrinolytic activation in trauma patients","volume":"11","author":"Raza","year":"2013","journal-title":"J. Thromb. Haemost."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"A5","DOI":"10.1186\/1757-7241-22-S1-A5","article-title":"Fibrinogen replacement in trauma haemorrhage","volume":"22","author":"Curry","year":"2014","journal-title":"Scand. J. Trauma Resusc. Emerg. Med."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Nencini, F., Bettiol, A., Argento, F.R., Borghi, S., Giurranna, E., Emmi, G., Prisco, D., Taddei, N., Fiorillo, C., and Becatti, M. (2024). Post-translational modifications of fibrinogen: Implications for clotting, fibrin structure and degradation. Mol. Biomed., 5.","DOI":"10.1186\/s43556-024-00214-x"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0140-6736(10)60835-5","article-title":"Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): A randomised, placebo-controlled trial","volume":"376","author":"Collaborators","year":"2010","journal-title":"Lancet"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Innerhofer, N., Treichl, B., Rugg, C., Fries, D., Mittermayr, M., Hell, T., Oswald, E., Innerhofer, P., and on behalf of the RETIC Study Group (2021). First-Line Administration of Fibrinogen Concentrate in the Bleeding Trauma Patient: Searching for Effective Dosages and Optimal Post-Treatment Levels Limiting Massive Transfusion\u2014Further Results of the RETIC Study. J. Clin. Med., 10.","DOI":"10.3390\/jcm10173930"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1097\/TA.0000000000003728","article-title":"Fibrinogen supplementation for the trauma patient: Should you choose fibrinogen concentrate over cryoprecipitate?","volume":"93","author":"Obaid","year":"2022","journal-title":"J. Trauma. Acute Care Surg."},{"key":"ref_65","unstructured":"Wormer, K.C., Jamil, R.T., and Bryant, S.B. (2024, October 22). Acute Postpartum Hemorrhage, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/29763164\/."},{"key":"ref_66","first-page":"1814","article-title":"Treatment of Obstetric Hemorrhage with Fibrinogen Concentrate","volume":"25","author":"Sahin","year":"2019","journal-title":"Med. Sci. Monit. Int. Med. J. Exp. Clin. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1056\/NEJMra1513247","article-title":"Postpartum Hemorrhage","volume":"384","author":"Bienstock","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1111\/anae.14628","article-title":"Four years\u2019 experience of a ROTEM \u00ae-guided algorithm for treatment of coagulopathy in obstetric haemorrhage","volume":"74","author":"McNamara","year":"2019","journal-title":"Anaesthesia"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1093\/bja\/aeu444","article-title":"Pre-emptive treatment with fibrinogen concentrate for postpartum haemorrhage: Randomized controlled trial","volume":"114","author":"Edwards","year":"2015","journal-title":"Br. J. Anaesth."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.bpa.2022.10.002","article-title":"The role of fibrinogen in postpartum hemorrhage","volume":"36","author":"Vermeulen","year":"2022","journal-title":"Best. Pract. Res. Clin. Anaesthesiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1111\/vox.12417","article-title":"Cryoprecipitate AHF vs. fibrinogen concentrates for fibrinogen replacement in acquired bleeding patients\u2014An economic evaluation","volume":"111","author":"Okerberg","year":"2016","journal-title":"Vox Sang."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/s12959-023-00540-0","article-title":"Tranexamic acid for haemostasis and beyond: Does dose matter?","volume":"21","author":"Lam","year":"2023","journal-title":"Thromb. J."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1056\/NEJMoa2028788","article-title":"Tranexamic Acid for the Prevention of Blood Loss after Cesarean Delivery","volume":"384","author":"Sentilhes","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"100","DOI":"10.12688\/wellcomeopenres.14722.1","article-title":"Effect of tranexamic acid on coagulation and fibrinolysis in women with postpartum haemorrhage (WOMAN-ETAC): A single-centre, randomised, double-blind, placebo-controlled trial","volume":"3","author":"Roberts","year":"2018","journal-title":"Wellcome Open Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1001\/jama.2019.17312","article-title":"Effect of Fibrinogen Concentrate vs Cryoprecipitate on Blood Component Transfusion After Cardiac Surgery","volume":"322","author":"Callum","year":"2019","journal-title":"JAMA"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1093\/bja\/aev367","article-title":"Preoperative supplementation with fibrinogen concentrate in cardiac surgery: A randomized controlled study","volume":"116","author":"Jeppsson","year":"2016","journal-title":"Br. J. Anaesth."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1093\/bja\/aew169","article-title":"Randomized evaluation of fibrinogen vs placebo in complex cardiovascular surgery (REPLACE): A double-blind phase III study of haemostatic therapy","volume":"117","author":"Levy","year":"2016","journal-title":"Br. J. Anaesth."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1097\/TA.0000000000002624","article-title":"Effect of fibrinogen concentrate administration on early mortality in traumatic hemorrhagic shock: A propensity score analysis","volume":"88","author":"Hamada","year":"2020","journal-title":"J. Trauma. Acute Care Surg."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1055\/a-1227-8050","article-title":"Massive Hemorrhage: The Role of Whole Blood Viscoelastic Assays","volume":"40","author":"Scala","year":"2020","journal-title":"H\u00e4mostaseologie"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/s13054-023-04327-7","article-title":"The European guideline on management of major bleeding and coagulopathy following trauma: Sixth edition","volume":"27","author":"Rossaint","year":"2023","journal-title":"Crit. Care"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1016\/j.jtha.2023.01.008","article-title":"Assays to quantify fibrinolysis: Strengths and limitations. Communication from the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee on fibrinolysis","volume":"21","author":"Zheng","year":"2023","journal-title":"J. Thromb. Haemost."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Drotarova, M., Zolkova, J., Belakova, K.M., Brunclikova, M., Skornova, I., Stasko, J., and Simurda, T. (2023). Basic Principles of Rotational Thromboelastometry (ROTEM\u00ae) and the Role of ROTEM\u2014Guided Fibrinogen Replacement Therapy in the Management of Coagulopathies. Diagnostics, 13.","DOI":"10.3390\/diagnostics13203219"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1111\/anae.15662","article-title":"Viscoelastic haemostatic point-of-care assays in the management of postpartum haemorrhage: A narrative review","volume":"77","author":"Dias","year":"2022","journal-title":"Anaesthesia"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Bareille, M., Lecompte, T., Mullier, F., and Roullet, S. (2023). Are Viscoelastometric Assays of Old Generation Ready for Disposal? Comment on Volod et al. Viscoelastic Hemostatic Assays: A Primer on Legacy and New Generation Devices. J. Clin. Med. 2022, 11, 860. J. Clin. Med., 12.","DOI":"10.3390\/jcm12020477"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Reardon, B., Pasalic, L., and Favaloro, E.J. (2024). The Role of Viscoelastic Testing in Assessing Hemostasis: A Challenge to Standard Laboratory Assays?. J. Clin. Med., 13.","DOI":"10.3390\/jcm13123612"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1111\/bjh.15524","article-title":"The use of viscoelastic haemostatic assays in the management of major bleeding","volume":"182","author":"Curry","year":"2018","journal-title":"Br. J. Haematol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1213\/ANE.0000000000004422","article-title":"Assessment of Coagulation by Thromboelastography During Ongoing Postpartum Hemorrhage: A Retrospective Cohort Analysis","volume":"130","author":"Rigouzzo","year":"2020","journal-title":"Anesth. Analg."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1007\/s10877-021-00782-1","article-title":"Efficacy of sonorheometry point of the care device in determining low fibrinogen levels in pregnant blood: An invitro dilution and reconstitution study","volume":"36","author":"Kodali","year":"2021","journal-title":"J. Clin. Monit. Comput."},{"key":"ref_89","unstructured":"Baulig, W. (2025, January 01). Comparison of the Resonance Sonorheometry Based Quantra\u00ae System with Rotational Thromboelastometry ROTEM\u00ae Sigma in Cardiac Surgery\u2014A Prospective Observational Study. Available online: https:\/\/www.academia.edu\/67965645\/Comparison_of_the_resonance_sonorheometry_based_Quantra_system_with_rotational_thromboelastometry_ROTEM_sigma_in_cardiac_surgery_a_prospective_observational_study?."},{"key":"ref_90","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_91","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_92","doi-asserted-by":"crossref","first-page":"S136","DOI":"10.1111\/trf.17774","article-title":"Analyzing and modeling massive transfusion strategies and the role of fibrinogen\u2014How much is the patient actually receiving?","volume":"64","author":"Keltner","year":"2024","journal-title":"Transfusion"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/s13054-022-03940-2","article-title":"The impact of acquired coagulation factor XIII deficiency in traumatic bleeding and wound healing","volume":"26","author":"Kleber","year":"2022","journal-title":"Crit. Care"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1001\/jamasurg.2022.6818","article-title":"Cost-effectiveness of Fibrinogen Concentrate vs Cryoprecipitate for Treating Acquired Hypofibrinogenemia in Bleeding Adult Cardiac Surgical Patients","volume":"158","author":"Abrahamyan","year":"2023","journal-title":"JAMA Surg."},{"key":"ref_95","unstructured":"National Clinical Guideline Centre (UK) (2025, January 30). Blood Transfusion. London: National Institute for Health and Care Excellence (NICE); 2015 Nov. (NICE Guideline, No. 24.) Appendix N, Unit Costs, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK338809\/."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"E179","DOI":"10.1002\/ajh.26940","article-title":"United States blood pricing: A cross-sectional analysis of charges and reimbursement at 200 US hospitals","volume":"98","author":"Jacobs","year":"2023","journal-title":"Am. J. Hematol."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Guerriero, C., Cairns, J., Perel, P., Shakur, H., and Roberts, I. (2011). Cost-Effectiveness Analysis of Administering Tranexamic Acid to Bleeding Trauma Patients Using Evidence from the CRASH-2 Trial. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0018987"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Volod, O., Bunch, C.M., Zackariya, N., Moore, E.E., Moore, H.B., Kwaan, H.C., Neal, M.D., Al-Fadhl, M.D., Patel, S.S., and Wiarda, G. (2022). Viscoelastic Hemostatic Assays: A Primer on Legacy and New Generation Devices. J. Clin. Med., 11.","DOI":"10.3390\/jcm11030860"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"3295","DOI":"10.1111\/trf.15437","article-title":"Fibrinogen concentrate for perioperative bleeding: What can we learn from the clinical trials?","volume":"59","author":"Cushing","year":"2019","journal-title":"Transfusion"},{"key":"ref_100","first-page":"951","article-title":"Preconditions of Hemostasis in Trauma: A Review. The Influence of Acidosis, Hypocalcemia, Anemia, and Hypothermia on Functional Hemostasis in Trauma","volume":"65","author":"Lier","year":"2008","journal-title":"J. Trauma Inj. Infect. Crit. Care"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1111\/j.1537-2995.2011.03247.x","article-title":"Transfusion-associated circulatory overload after plasma transfusion","volume":"52","author":"Narick","year":"2011","journal-title":"Transfusion"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"e258","DOI":"10.1016\/S2352-3026(17)30077-7","article-title":"Reversal of trauma-induced coagulopathy using first-line coagulation factor concentrates or fresh frozen plasma (RETIC): A single-centre, parallel-group, open-label, randomised trial","volume":"4","author":"Innerhofer","year":"2017","journal-title":"Lancet Haematol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1016\/j.ajem.2018.02.018","article-title":"The effect of fibrinogen concentrate and fresh frozen plasma on the outcome of patients with acute traumatic coagulopathy: A quasi-experimental study","volume":"36","author":"Akbari","year":"2018","journal-title":"Am. J. Emerg. Med."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Stanford, S., Roy, A., Cecil, T., Hegener, O., Schulz, P., Turaj, A., Lim, S., and Arbuthnot, E. (2023). Differences in coagulation-relevant parameters: Comparing cryoprecipitate and a human fibrinogen concentrate. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0290571"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"e036416","DOI":"10.1136\/bmjopen-2019-036416","article-title":"Effect of early cryoprecipitate transfusion versus standard care in women who develop severe postpartum haemorrhage (ACROBAT) in the UK: A protocol for a pilot cluster randomised trial","volume":"10","author":"Green","year":"2020","journal-title":"BMJ Open"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1111\/anae.15595","article-title":"Early cryoprecipitate transfusion versus standard care in severe postpartum haemorrhage: A pilot cluster-randomised trial","volume":"77","author":"Green","year":"2021","journal-title":"Anaesthesia"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Kamidani, R., Miyake, T., Okada, H., Yoshimura, G., Kusuzawa, K., Miura, T., Shimaoka, R., Oiwa, H., Yamaji, F., and Mizuno, Y. (2021). Effect of cryoprecipitate transfusion therapy in patients with postpartum hemorrhage: A retrospective cohort study. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-97954-5"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.bja.2022.05.012","article-title":"Impact of cardiopulmonary bypass duration on efficacy of fibrinogen replacement with cryoprecipitate compared with fibrinogen concentrate: A post hoc analysis of the Fibrinogen Replenishment in Surgery (FIBRES) randomised controlled trial","volume":"129","author":"Bartoszko","year":"2022","journal-title":"Br. J. Anaesth."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"e020741","DOI":"10.1136\/bmjopen-2017-020741","article-title":"Protocol for a phase III, non-inferiority, randomised comparison of a new fibrinogen concentrate versus cryoprecipitate for treating acquired hypofibrinogenaemia in bleeding cardiac surgical patients: The FIBRES trial","volume":"8","author":"Karkouti","year":"2018","journal-title":"BMJ Open"},{"key":"ref_110","first-page":"171","article-title":"Targeted fibrinogen concentrate use in severe traumatic haemorrhage","volume":"21","author":"Seebold","year":"2019","journal-title":"Crit. Care Resusc."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3310\/hta17100","article-title":"The CRASH-2 trial: A randomised controlled trial and economic evaluation of the effects of tranexamic acid on death, vascular occlusive events and transfusion requirement in bleeding trauma patients","volume":"17","author":"Roberts","year":"2013","journal-title":"Health Technol. Assess."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1016\/S0140-6736(19)32233-0","article-title":"Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): A randomised, placebo-controlled trial","volume":"394","author":"Roberts","year":"2019","journal-title":"Lancet"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.annemergmed.2023.10.004","article-title":"Tranexamic Acid for Traumatic Injury in the Emergency Setting: A Systematic Review and Bias-Adjusted Meta-Analysis of Randomized Controlled Trials","volume":"83","author":"Fouche","year":"2023","journal-title":"Ann. Emerg. Med."},{"key":"ref_114","unstructured":"Ageron, F.-X.D. (2021). Tranexamic Acid in Trauma Care: Who Should Be Treated, When and Where?. [Ph.D. Thesis, London School of Hygiene & Tropical Medicine]."},{"key":"ref_115","first-page":"e52111","article-title":"Effectiveness of Tranexamic Acid in Trauma Patients: A Systematic Review","volume":"16","author":"Monge","year":"2024","journal-title":"Cureus"},{"key":"ref_116","first-page":"CD007872","article-title":"Tranexamic acid for preventing postpartum haemorrhage after vaginal birth","volume":"1","author":"Rohwer","year":"2025","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_117","first-page":"CD016278","article-title":"Tranexamic acid for preventing postpartum haemorrhage after caesarean section","volume":"2024","author":"Rohwer","year":"2024","journal-title":"Cochrane Libr."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1055\/a-2052-9175","article-title":"Blood coagulation and beyond: Position paper from the Fourth Maastricht Consensus Conference on Thrombosis","volume":"123","author":"Akbulut","year":"2023","journal-title":"Thromb. Haemost."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1213\/ANE.0000000000005513","article-title":"Pro-Con Debate: Fibrinogen Concentrate or Cryoprecipitate for Treatment of Acquired Hypofibrinogenemia in Cardiac Surgical Patients","volume":"133","author":"Hensley","year":"2021","journal-title":"Anesth. Analg."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1097\/SHK.0000000000000161","article-title":"Elevated Tissue Plasminogen Activator and Reduced Plasminogen Activator Inhibitor Promote Hyperfibrinolysis in Trauma Patients","volume":"41","author":"Cardenas","year":"2014","journal-title":"Shock"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1097\/TA.0b013e31825c1234","article-title":"Hyperfibrinolysis at admission is an uncommon but highly lethal event associated with shock and prehospital fluid administration","volume":"73","author":"Cotton","year":"2012","journal-title":"J. Trauma Acute Care Surg."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/S1462399402004362","article-title":"Recent advances in understanding endogenous fibrinolysis: Implications for molecular-based treatment of vascular disorders","volume":"4","author":"Bodary","year":"2002","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1097\/EJA.0000000000001632","article-title":"Efficacy and safety of aprotinin in paediatric cardiac surgery","volume":"39","author":"Atasever","year":"2022","journal-title":"Eur. J. Anaesthesiol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1097\/EJA.0000000000001710","article-title":"Use and safety of aprotinin in routine clinical practice","volume":"39","author":"Ouattara","year":"2022","journal-title":"Eur. J. Anaesthesiol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"ezae038","DOI":"10.1093\/ejcts\/ezae038","article-title":"Retrospective aprotinin cardiac surgical studies and their limitations: Time for a prospective randomized clinical trial","volume":"65","author":"Erdoes","year":"2024","journal-title":"Eur. J. Cardio-Thorac. Surg."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s43019-020-00079-8","article-title":"Prospective randomized trial comparing efficacy and safety of intravenous and intra-articular tranexamic acid in total knee arthroplasty","volume":"32","author":"Li","year":"2020","journal-title":"Knee Surg. Relat. Res."},{"key":"ref_127","unstructured":"(2025, January 01). Annals Admin Association Between Genetic Polymorphisms in Fibrinogen Genes and Bleeding Risk in Patients Treated with Direct Oral Anticoagulants\u2014Annals Singapore. Available online: https:\/\/annals.edu.sg\/association-between-genetic-polymorphisms-in-fibrinogen-genes-and-bleeding-risk-in-patients-treated-with-direct-oral-anticoagulants\/."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1016\/j.jacc.2008.06.016","article-title":"Common Genetic Polymorphisms and Haplotypes of Fibrinogen Alpha, Beta, and Gamma Chains Affect Fibrinogen Levels and the Response to Proinflammatory Stimulation in Myocardial Infarction Survivors: The AIRGENE Study","volume":"52","author":"Jacquemin","year":"2008","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1136\/emermed-2019-209181","article-title":"Biological mechanisms and individual variation in fibrinolysis after major trauma","volume":"37","author":"Coats","year":"2020","journal-title":"Emerg. Med. J."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"2248","DOI":"10.1182\/blood.2023022596","article-title":"Whole-genome analysis of plasma fibrinogen reveals population-differentiated genetic regulators with putative liver roles","volume":"144","author":"Huffman","year":"2024","journal-title":"Blood"},{"key":"ref_131","first-page":"657","article-title":"Antifibrinolytic Therapy and Perioperative Considerations","volume":"128","author":"Levy","year":"2018","journal-title":"Anesthesiol. J. Am. Soc. Anesthesiol."},{"key":"ref_132","unstructured":"(2025, January 01). Congenital Fibrinogen Deficiency via the FGG Gene Test\u2014PreventionGenetics. Available online: https:\/\/www.preventiongenetics.com\/testInfo?val=Congenital-Fibrinogen-Deficiency-via-the-FGG-Gene."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1182\/blood-2018-06-856195","article-title":"Affimer proteins as a tool to modulate fibrinolysis, stabilize the blood clot, and reduce bleeding complications","volume":"133","author":"Kearney","year":"2019","journal-title":"Blood"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1182\/bloodadvances.2024014235","article-title":"Use of Affimer Technology for Inhibition of \u03b12-antiplasmin and Enhancement of Fibrinolysis","volume":"9","author":"Pechlivani","year":"2024","journal-title":"Blood Adv."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"e24903","DOI":"10.7554\/eLife.24903","article-title":"Affimer proteins are versatile and renewable affinity reagents","volume":"6","author":"Tiede","year":"2017","journal-title":"eLife"},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Pechlivani, N., Kearney, K.J., Tiede, C., Cheah, R., Phoenix, F., Ponnambalam, S., Ault, J.R., McPherson, M.J., Tomlinson, D.C., and Ajjan, R.A. (2022). Affinity purification of fibrinogen using an Affimer column. Biochim. Biophys. Acta (BBA)-Gen. Subj., 1866.","DOI":"10.1016\/j.bbagen.2022.130115"},{"key":"ref_137","unstructured":"(2025, January 01). Good Manufacturing Practice|European Medicines Agency (EMA). Available online: https:\/\/www.ema.europa.eu\/en\/human-regulatory-overview\/research-development\/compliance-research-development\/good-manufacturing-practice?utm_source=chatgpt.com."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.1016\/j.jtha.2024.03.001","article-title":"A novel method to quantify fibrin\u2013fibrin and fibrin\u2013\u03b12-antiplasmin cross-links in thrombi formed from human trauma patient plasma","volume":"22","author":"Morrow","year":"2024","journal-title":"J. Thromb. Haemost."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"e396","DOI":"10.1055\/a-1957-6817","article-title":"Plasmin Inhibitor in Health and Diabetes: Role of the Protein as a Therapeutic Target","volume":"6","author":"Alsayejh","year":"2022","journal-title":"TH Open"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1530\/EOR-22-0054","article-title":"Coagulopathy management of multiple injured patients\u2014A comprehensive literature review of the European guideline 2019","volume":"7","author":"Niemann","year":"2022","journal-title":"EFORT Open Rev."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1093\/bjs\/znab117.001","article-title":"O1: Discovering Novel Therapeutics to Treat Acute Traumatic Coagulopathy (ATC)","volume":"108","author":"Thaventhiran","year":"2021","journal-title":"Br. J. Surg."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/3\/1336\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:27:02Z","timestamp":1760027222000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/3\/1336"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,5]]},"references-count":141,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["ijms26031336"],"URL":"https:\/\/doi.org\/10.3390\/ijms26031336","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,5]]}}}