{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T23:02:50Z","timestamp":1789772570114,"version":"4.0.1"},"reference-count":19,"publisher":"Georg Thieme Verlag KG","issue":"07","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Drug Res (Stuttg)"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Human fibrinogen concentrate is used as replacement therapy for congenital\nand acquired fibrinogen deficiencies. Despite similar manufacturing\nprinciples, compositional differences among products may affect clot quality\nand hemostatic efficacy. BT524 (Biotest) is a newly developed human\nfibrinogen concentrate with proven clinical safety and efficacy.<\/jats:p>\n                  <jats:p>The objective of this study was to compare the biochemical composition and in\nvitro functional characteristics of BT524 with those of two commercially\navailable plasma-derived fibrinogen concentrates (Products I and II).<\/jats:p>\n                  <jats:p>Three independent batches of each human fibrinogen concentrate were analyzed\nfor the total and clottable protein, fibrinogen antigen, fibrinogen activity\nby Clauss, clotting factors, degradation markers (fibrinopeptide A and\nD-dimer), sub-visible particles, and aggregates. Maximum clot firmness and\ndynamics were assessed using rotational thromboelastometry (fibrin-based\nthromboelastometry). Fibrinogen deficient plasma with low factor XIII\ncontent was spiked each fibrinogen concentrate and increasing concentrations\nof factor XIII (0\u20130.8 U\/mL).<\/jats:p>\n                  <jats:p>BT524 showed consistent fibrinogen content but contained no active factor\nVIII, factor XIII, or von Willebrand factor, indicating a precisely defined\ncomposition. Levels of degradation markers, aggregates, and sub-visible\nparticles were markedly lower than in comparator products, reflecting the\nsuperior biochemical purity of BT524. BT524 achieved significantly higher\nmaximum clot firmness than Product I (p&lt;0.0001) and demonstrated\ncomparable performance with Product II. Spiking of factor XIII resulted in\nan additional increase in maximum clot firmness in BT524 and Product II, but\nnot in Product I, proving functional factor XIII susceptibility of\nBT524.<\/jats:p>\n                  <jats:p>BT524 demonstrates high biochemical purity and robust functional clot\nformation. These findings highlight that fibrinogen concentrates differ in\ncomposition, functionality and molecular integrity, which determines clot\nquality and hemostatic performance.<\/jats:p>","DOI":"10.1055\/a-2869-0130","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T22:48:31Z","timestamp":1782341311000},"page":"179-185","source":"Crossref","is-referenced-by-count":0,"title":["Comparative Biochemical and Functional Characterization of a Novel\nHuman Fibrinogen Concentrate (BT524) and Established Plasma-Derived Fibrinogen\nConcentrates"],"prefix":"10.1055","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4328-849X","authenticated-orcid":false,"given":"Michaela","family":"Bergmann","sequence":"additional","affiliation":[{"name":"Biotest, Dreieich, Germany","department":["Investigational and Applied Biosciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"R\u00fcbsamen","sequence":"additional","affiliation":[{"name":"Biotest, Dreieich, Germany","department":["Investigational and Applied Biosciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Kistner","sequence":"additional","affiliation":[{"name":"Biotest, Dreieich, Germany","department":["Investigational and Applied Biosciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.biologicals.2017.12.003","article-title":"Biochemical characterization, stability, and pathogen safety of a new fibrinogen\nconcentrate (fibryga\u00ae)","volume":"52","author":"P M Schulz","year":"2018","journal-title":"Biologicals"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1111\/hae.13876","article-title":"Fibrinogen concentrates in hereditary fibrinogen disorders: Past, present and\nfuture","volume":"26","author":"A Casini","year":"2020","journal-title":"Haemophilia"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/26348535211064621","article-title":"Quality Attributes of Plasma Derived Human Fibrinogen (Fibrogen-I\u00ae)","volume":"15","author":"S Dolia","year":"2021","journal-title":"Plasmatology"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"e0290571","DOI":"10.1371\/journal.pone.0290571","article-title":"Differences in coagulation-relevant parameters: Comparing cryoprecipitate and a\nhuman fibrinogen concentrate","volume":"18","author":"S Stanford","year":"2023","journal-title":"PLoS One"},{"issue":"11","key":"ref5","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1111\/trf.18434","article-title":"Survey of cryoprecipitate production and cryoprecipitate and fibrinogen\nconcentrate utilization in North America: Variable practices observed from July\n2016 to June 2021, The BEST Collaborative Study","volume":"65","author":"W Lu","year":"2025","journal-title":"Transfusion"},{"key":"ref6","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\nfibrinogen concentrates","volume":"205","author":"A Neisser-Svae","year":"2021","journal-title":"Thromb Res"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1391422","DOI":"10.3389\/fmed.2024.1391422","article-title":"Are all fibrinogen concentrates the same? The effects of two fibrinogen\ntherapies in an afibrinogenemic patient and in a fibrinogen deficient plasma\nmodel. A clinical and laboratory case report","volume":"11","author":"S Goodarzi","year":"2024","journal-title":"Front Med (Lausanne)"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"103264","DOI":"10.1016\/j.eclinm.2025.103264","article-title":"Efficacy and safety of human fibrinogen concentrate (BT524) in patients with\nmajor haemorrhage undergoing major orthopaedic or abdominal surgery (AdFIrst): a\nrandomised, active-controlled, multicentre, partially blinded, phase 3\nnon-inferiority trial","author":"N Rahe-Meyer","year":"2025","journal-title":"eClinicalMedicine"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1182\/blood-2024-198116","article-title":"Evaluation of Pharmacokinetics, Efficacy and Safety of a New Human Fibrinogen\nConcentrate in Patients with Congenital Fibrinogen Deficiency","volume":"144","author":"C D Khayat","year":"2024","journal-title":"Blood"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1055\/a-2715-2994","article-title":"Pharmacokinetics, Hemostatic Efficacy, and Safety of a New Human Fibrinogen\nConcentrate in Adult and Pediatric Patients with Congenital Fibrinogen\nDeficiency.","author":"C Djambas Khayat","year":"2025","journal-title":"Thromb Haemost"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1159\/000502016","article-title":"Comparison of Two Different Fibrinogen Concentrates in an in vitro Model of\nDilutional Coagulopathy","volume":"47","author":"P Groene","year":"2020","journal-title":"Transfus Med Hemother"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1111\/ijlh.14201","article-title":"International council for standardisation in haematology recommendations on\nfibrinogen assays, thrombin clotting time and related tests in the investigation\nof bleeding disorders","volume":"46","author":"I Mackie","year":"2024","journal-title":"Int J Lab Hematol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"617500","DOI":"10.3389\/fped.2021.617500","article-title":"Pediatric Fibrinogen PART I-Pitfalls in Fibrinogen Evaluation and Use of\nFibrinogen Replacement Products in Children","volume":"9","author":"E J Huisman","year":"2021","journal-title":"Front Pediatr"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/S0049-3848(00)00344-3","article-title":"Discrepancy between fibrinogen concentrations determined by clotting rate and\nclottability assays during the acute-phase reaction","volume":"100","author":"T Jensen","year":"2000","journal-title":"Thromb Res"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1111\/ijlh.13147","article-title":"Effects of hemolysis, bilirubin, and lipemia interference on coagulation tests\ndetected by two analytical systems","volume":"42","author":"C Nougier","year":"2020","journal-title":"Int J Lab Hematol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"122490","DOI":"10.1016\/j.ijpharm.2022.122490","article-title":"In vitro and in vivo immunogenicity assessment of protein aggregate\ncharacteristics","volume":"631","author":"C Thorlaksen","year":"2023","journal-title":"Int J Pharm"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s13049-014-0073-z","article-title":"Correction of hypothermic and dilutional coagulopathy with concentrates of\nfibrinogen and factor XIII: an in vitro study with ROTEM","volume":"22","author":"D Winstedt","year":"2014","journal-title":"Scand J Trauma Resusc Emerg Med"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1007\/978-3-319-49674-0_13","article-title":"Fibrin Formation, Structure and Properties","volume":"82","author":"J W Weisel","year":"2017","journal-title":"Subcell Biochem"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.thromres.2024.03.004","article-title":"Fundamental considerations for designing endothelialized in vitro models\nof thrombosis","volume":"236","author":"T P Lemmens","year":"2024","journal-title":"Thromb Res"}],"container-title":["Drug Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2869-0130.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T22:32:22Z","timestamp":1789770742000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2869-0130"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,24]]},"references-count":19,"journal-issue":{"issue":"07","published-online":{"date-parts":[[2026,9,18]]},"published-print":{"date-parts":[[2026,9]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2869-0130","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["2194-9379","2194-9387"],"issn-type":[{"value":"2194-9379","type":"print"},{"value":"2194-9387","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,24]]}}}