{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T01:12:28Z","timestamp":1747185148876,"version":"3.40.5"},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,4,23]],"date-time":"2020-04-23T00:00:00Z","timestamp":1587600000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Grifols"},{"name":"University of Bari"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Plasma\u2010derived FVIII\/VWF complex was reported to be less sensitive to inhibitors than FVIII preparations devoid of VWF.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To compare the efficacy of FVIII\/VWF complex (Fanhdi) and five different VWF\u2010free FVIII preparations in restoring thrombin generation and activation of thrombin\u2010activatable fibrinolysis inhibitor (TAFI) in haemophilic plasma, with and without inhibitor, and in cell\u2010based models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Experiments were performed in haemophilic plasma supplemented with inhibitory IgG or in plasma samples obtained from haemophilia A patients without (n\u00a0=\u00a011) and with inhibitor (n\u00a0=\u00a012). Thrombin generation was evaluated by calibrated automated thrombography (CAT) under standard conditions, in the presence of activated protein C (APC) or thrombomodulin (TM), and in cell\u2010based models including endothelial cells, either alone or in combination with platelets or tissue factor\u2010expressing blood mononuclear cells. The kinetics of TAFI activation was determined by a two\u2010stage functional assay in the absence and in the presence of APC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In haemophilic plasma without inhibitor, Fanhdi enhanced thrombin generation and TAFI activation as well as recombinant (2nd\u20104th generation) and plasma\u2010derived FVIII preparations devoid of VWF. On the contrary, in plasma with inhibitor, Fanhdi displayed a greater ability to restore thrombin generation and TAFI activation under all tested conditions. Notably, in cell\u2010based models including endothelial cells, Fanhdi proved more efficient than all other preparations in improving thrombin generation even in the absence of inhibitor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The greater pro\u2010haemostatic activity of FVIII\/VWF complex, either in haemophilic plasma with inhibitor or in the presence of endothelial cells, may offer therapeutic advantages.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.14008","type":"journal-article","created":{"date-parts":[[2020,4,23]],"date-time":"2020-04-23T22:35:29Z","timestamp":1587681329000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["FVIII\/VWF complex displays a greater pro\u2010haemostatic activity than FVIII preparations devoid of VWF: Study in plasma and cell\u2010based models"],"prefix":"10.1111","volume":"26","author":[{"given":"Concetta T.","family":"Ammollo","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences and Human Oncology University of Bari Aldo Moro Bari Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabrizio","family":"Semeraro","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Human Oncology University of Bari Aldo Moro Bari Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonia","family":"Vitulli","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Human Oncology University of Bari Aldo Moro Bari Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lavinia","family":"Dirienzo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Human Oncology University of Bari Aldo Moro Bari Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna M.","family":"Mezzasoma","sequence":"additional","affiliation":[{"name":"Section of Internal and Cardiovascular Medicine Department of Medicine University of Perugia Perugia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Semeraro","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Human Oncology University of Bari Aldo Moro Bari Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Gresele","sequence":"additional","affiliation":[{"name":"Section of Internal and Cardiovascular Medicine Department of Medicine University of Perugia Perugia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9146-8095","authenticated-orcid":false,"given":"Mario","family":"Colucci","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Human Oncology University of Bari Aldo Moro Bari Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,4,23]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI110479"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.111.230631"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.28.16603"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V88.10.3815.bloodjournal88103815"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1616530"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-01-828434"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)01123-X"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2007.02572.x"},{"key":"e_1_2_9_10_1","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1046\/j.1365-2516.2003.00780.x","article-title":"The epidemiology of inhibitors in haemophilia A: a systematic review","volume":"9","author":"Wight J","year":"2003","journal-title":"Haemophilia"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2010.03899.x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2006.01400.x"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12494"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2018.12.007"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1650655"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2007.01577.x"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2010.04120.x"},{"key":"e_1_2_9_18_1","first-page":"529","article-title":"Direct induction of tissue factor synthesis by endotoxin in human macrophages from diverse anatomical sites","volume":"50","author":"Semeraro N","year":"1983","journal-title":"Immunology"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1159\/000071636"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2017.08.012"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2010.03739.x"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12431"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.1996.tb00022.x"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2001.00530.x"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2001.00526.x"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2516.2003.00802.x"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113721"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.124.3_suppl.26S"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.10333"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M401027200"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2004.00605.x"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-05-577643"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12181"}],"container-title":["Haemophilia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fhae.14008","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.14008","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/hae.14008","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.14008","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,3]],"date-time":"2023-09-03T05:36:22Z","timestamp":1693719382000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hae.14008"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,23]]},"references-count":32,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,7]]}},"alternative-id":["10.1111\/hae.14008"],"URL":"https:\/\/doi.org\/10.1111\/hae.14008","archive":["Portico"],"relation":{},"ISSN":["1351-8216","1365-2516"],"issn-type":[{"type":"print","value":"1351-8216"},{"type":"electronic","value":"1365-2516"}],"subject":[],"published":{"date-parts":[[2020,4,23]]},"assertion":[{"value":"2019-11-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}