{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T13:02:20Z","timestamp":1784898140393,"version":"3.55.0"},"reference-count":40,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Various extended half\u2010life recombinant factor VIII (EHL\u2010FVIII) products have been designed to improve the pharmacokinetic properties of FVIII, allowing prolonged haemostatic coverage and reducing the injection burden in people with haemophilia A. Nevertheless, the influence of direct molecular attachment on fibrin clot formation and stability remains to be investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To investigate the stability and architecture of fibrin clots in the presence of various types of EHL\u2010FVIII.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Three EHL\u2010FVIII products with direct attachment modifications (damoctocog alfa pegol, efraloctocog alfa, and rurioctocog alfa pegol) and two standard FVIII (turoctocog alfa and rurioctocog alfa) were added to FVIII\u2010deficient whole blood and plasma at various concentrations for functional comparison. Under whole\u2010blood conditions, functional assays were performed using rotational thromboelastometry (ROTEM) and a microchip flow\u2010chamber system (T\u2010TAS). Under plasma\u2010based conditions, fibrin fibres were directly observed by electron microscopy and coagulation function was assessed using clot waveform analysis (CWA). Anticoagulant and fibrinolytic activities were evaluated by CWA with the addition of activated protein C and tissue plasminogen activator, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>At equivalent activity levels, none of the assays revealed significant differences among the three EHL products or the two standard products. All contributed comparably to fibrin clot formation and stability, as well as to anticoagulation and fibrinolysis functions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Direct modification by PEGylation or IgG\u2010Fc fusion to impart EHL characteristics preserves the functional properties of native FVIII.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain Language Summary<\/jats:title>\n                    <jats:p>People with haemophilia A require treatment with factor VIII (FVIII) to prevent or control bleeding. Some FVIII products are designed to remain active in the body for a longer time, which can reduce the number of injections needed. This extended half\u2010life is achieved by chemically or biologically modifying FVIII, for example by attaching polyethylene glycol (PEG) or the Fc portion of immunoglobulin G. These treatments are known as extended half\u2010life FVIII (EHL\u2010FVIII) products. However, it has not been fully established whether these modifications affect how blood clots form and remain stable. In this study, we compared three EHL\u2010FVIII products with two standard FVIII products using FVIII\u2010deficient blood and plasma. We evaluated clot formation and stability using several laboratory techniques, including whole\u2010blood assays and scanning electron microscopy. We also examined potential differences in anticoagulant and fibrinolytic properties. At comparable FVIII activity levels, we observed no major differences between the EHL\u2010FVIII products and the standard FVIII products in any of the assays performed. These findings suggest that PEGylation or Fc fusion, which are used to extend the half\u2010life of FVIII, do not impair its functional properties related to fibrin clot formation and stability.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/hae.70361","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T12:12:18Z","timestamp":1784895138000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Extended Half\u2010Life Recombinant Factor VIII Conjugated with Modifying Substances Does Not Affect Fibrin Clot Formation or Stability in Haemophilia A Blood Samples"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0157-5215","authenticated-orcid":false,"given":"Naruto","family":"Shimonishi","sequence":"first","affiliation":[{"name":"Department of Pediatrics Nara Medical University  Nara Japan"},{"name":"The Course of Thrombosis and Hemostasis Molecular Pathology Nara Medical University  Nara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiji","family":"Nogami","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Nara Medical University  Nara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa067659"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538\u20107836.2011.04214.x"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(11)61139\u20102"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365\u20102516.2002.00695.x"},{"issue":"10","key":"e_1_2_13_6_1","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1177\/2040620717721458","article-title":"Current and Emerging Factor VIII Replacement Products for Hemophilia A","volume":"8","author":"Cafuir L. 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