{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T01:11:35Z","timestamp":1747185095635,"version":"3.40.5"},"reference-count":23,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T00:00:00Z","timestamp":1694649600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL126974"],"award-info":[{"award-number":["R01HL126974"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction and aim<\/jats:title><jats:p>Severe haemophilia B (HB) is characterized by spontaneous bleeding episodes, mostly into joints. Recurrent bleeds lead to progressive joint destruction called haemophilic arthropathy. The current concept of prophylaxis aims at maintaining the FIX level &gt;3\u20135\u00a0IU\/dL, which is effective at reducing the incidence of haemophilic arthropathy. Extended half\u2010life FIX molecules make it easier to achieve these target trough levels compared to standard FIX concentrates. We previously reported that the fusion of a recombinant FIX (rFIX) to factor XIII\u2010B (FXIIIB) subunit prolonged the half\u2010life of the rFIX\u2010LXa\u2010FXIIIB fusion molecule in mice and rats 3.9\u2010 and 2.2\u2010fold, respectively, compared with rFIX\u2010WT. However, the mechanism behind the extended half\u2010life was not known.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>Mass spectrometry and ITC were used to study interactions of rFIX\u2010LXa\u2010FXIIIB with albumin. Pharmacokinetic analyses in fibrinogen\u2010KO and FcRn\u2010KO mice were performed to evaluate the effect of albumin and fibrinogen on in\u2010vivo half\u2010life of rFIX\u2010LXa\u2010FXIIIB. Finally saphenous vein bleeding model was used to assess in\u2010vivo haemostatic activity of rFIX\u2010LXa\u2010FXIIIB.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and conclusion<\/jats:title><jats:p>We report here the key interactions that rFIX\u2010LXa\u2010FXIIIB may have in plasma are with fibrinogen and albumin which may mediate its prolonged half\u2010life. In addition, using the saphenous vein bleeding model, we demonstrate that rFIX\u2010FXIIIB elicits functional clot formation that is indistinguishable from that of rFIX\u2010WT.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.14855","type":"journal-article","created":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T17:49:57Z","timestamp":1694713797000},"page":"1483-1489","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Characterization of a recombinant factor IX molecule fused to coagulation factor XIII\u2010B subunit"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0455-0248","authenticated-orcid":false,"given":"Stephanie","family":"Desage","sequence":"first","affiliation":[{"name":"UR4609 \u2013 Hemostase et Thrombose Universite Claude Bernard Lyon I  Lyon France"},{"name":"Unite d'Hemostase Clinique, Hopital Cardiologique Hospices Civils de Lyon  Lyon 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