{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T19:00:44Z","timestamp":1770750044720,"version":"3.50.0"},"reference-count":17,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,8,4]],"date-time":"2022-08-04T00:00:00Z","timestamp":1659571200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100016300","name":"Octapharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100016300","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Congenital afibrinogenaemia and hypofibrinogenaemia are rare coagulation disorders where clotting is impaired due to a lack of fibrinogen. Consequent bleeding episodes (BEs) are treated using human fibrinogen concentrate (HFC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>This post\u2010hoc analysis compared HFC pharmacokinetics (PK) and dosing between patient age groups and defined the in vivo recovery (IVR) for children with a\u2010 and hypofibrinogenaemia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The analysis used data from the FORMA\u201001 (Phase 2), FORMA\u201002 and FORMA\u201004 (Phase 3) multinational, prospective, open\u2010label studies in patients with a\u2010 and hypofibrinogenaemia. HFC PK in adults\/adolescents (\u226512 years; FORMA\u201001) and children (&lt;12 years; FORMA\u201004) was examined. Haemostatic efficacy in BE treatment and perioperative prophylaxis was examined in FORMA\u201002 and FORMA\u201004 using an objective 4\u2010point scale, with success defined as excellent\/good.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Median (range) age was 23 years for FORMA\u201001 (12\u201353; <jats:italic>n<\/jats:italic>\u00a0=\u00a022), 26.5 years for FORMA\u201002 (12\u201354; <jats:italic>n<\/jats:italic>\u00a0=\u00a025), and 6 years for FORMA\u201004 (1\u201310; <jats:italic>n<\/jats:italic>\u00a0=\u00a013). Mean PK parameters were lower for children (AUC, C<jats:sub>max<\/jats:sub>, IVR; <jats:italic>p<\/jats:italic>\u00a0=\u00a0.02), while clearance was higher. Median (range) total dose of HFC for all BEs was 59.41\u00a0mg\/kg (32.12\u2013273.80) in adults\/adolescents and was 24% higher (ns) in children at 73.91\u00a0mg\/kg (47.45\u2013262.50). Treatment was successful in 98.9% of the 89 BEs in adults\/adolescents and in 100% of the 10 BEs in children, with comparable results for perioperative prophylaxis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>As expected, HFC PK differed between adults\/adolescents and children. However, with the higher doses given to children, HFC showed similar efficacy across age groups. Dose adaptation based on age groups appears recommendable.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.14619","type":"journal-article","created":{"date-parts":[[2022,8,4]],"date-time":"2022-08-04T15:08:46Z","timestamp":1659625726000},"page":"1022-1032","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Analysis of fibrinogen concentrate pharmacokinetics and dosing for bleeds and surgery in adults, adolescents, and children with congenital afibrinogenaemia and hypofibrinogenaemia"],"prefix":"10.1111","volume":"28","author":[{"given":"Claudia","family":"Djambas Khayat","sequence":"first","affiliation":[{"name":"Hotel Dieu de France Hospital  Beirut Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sunil D.","family":"Lohade","sequence":"additional","affiliation":[{"name":"Sahyadri Specialty Hospital  Pune India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omid R.","family":"Zekavat","sequence":"additional","affiliation":[{"name":"Hematology Research Center Nemazee Hospital Shiraz University of Medical Sciences  Shiraz Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina","family":"Kruzhkova","sequence":"additional","affiliation":[{"name":"Research &amp; Development Department Octapharma  Lachen Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Solomon","sequence":"additional","affiliation":[{"name":"Research &amp; Development Department Octapharma  Lachen Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sigurd","family":"Knaub","sequence":"additional","affiliation":[{"name":"Research &amp; Development Department Octapharma  Lachen Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flora","family":"Peyvandi","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico Angelo Bianchi Bonomi Hemophilia and Thrombosis Center  Milan Italy"},{"name":"Department of Pathophysiology and Transplantation Universit\u00e0 degli Studi di Milano  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,8,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020009472"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2011.04424.x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/17474086.2018.1458610"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/EJA.0000000000000630"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14727"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14230"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.13923"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2009.03633.x"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14392"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2011.03066.x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0040-1710015"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics3010053"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12797"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13251"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.18773\/austprescr.2016.071"},{"key":"e_1_2_9_17_1","first-page":"549","article-title":"Weight\u2010based dosing in medication use: what should we know?","volume":"10","author":"Pan S\u2010D","year":"2016","journal-title":"Patient Prefer Adherence"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.14147"}],"container-title":["Haemophilia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.14619","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/hae.14619","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.14619","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T09:47:58Z","timestamp":1692524878000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hae.14619"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,4]]},"references-count":17,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,11]]}},"alternative-id":["10.1111\/hae.14619"],"URL":"https:\/\/doi.org\/10.1111\/hae.14619","archive":["Portico"],"relation":{},"ISSN":["1351-8216","1365-2516"],"issn-type":[{"value":"1351-8216","type":"print"},{"value":"1365-2516","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,4]]},"assertion":[{"value":"2022-02-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}