{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T13:26:12Z","timestamp":1789565172205,"version":"build-2803163510"},"reference-count":27,"publisher":"Georg Thieme Verlag KG","issue":"10","funder":[{"name":"GIRCI-HUGO","award":["Grant"],"award-info":[{"award-number":["Grant"]}]},{"name":"CoMETH","award":["Grant"],"award-info":[{"award-number":["Grant"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:p>\n            Background\u2003Desmopressin (DDAVP) is used in patients with moderate\/mild hemophilia A (PWMHs) to increase their factor VIII (FVIII) level and, if possible, normalize it. However, its effectiveness varies between individuals. The GIDEMHA study aims to investigate the influence of F8 gene variants.<\/jats:p><jats:p>\n            Material and Methods\u2003The study collected the trajectory of FVIII levels from therapeutic intravenous DDAVP tests in four French hemophilia treatment centers. A pharmacological analysis was performed associated with efficacy scores according to F8 variants: absolute and relative responses, as well as new scores: absolute duration (based on duration with FVIII \u2265 0.50\u2009IU.mL\u22121) and relative duration (based on half-life).<\/jats:p><jats:p>\n            Results\u2003From enrolled 439 PWMHs, 327 had a hot-spot F8 variant (with \u22655 PWMHs). For these, the median (min\u2013max) basal and peak FVIII were 0.20 (0.02\u20130.040) and 0.74 (0.14\u20132.18) IU.mL\u22121 respectively, with FVIII recovery being 3.80\u2009IU.ml\u22121 (1.15\u201314.75). The median FVIII half-life was 3.9\u2009hours (0.7\u201315.9\u2009hours). FVIII was normalized (\u22650.50\u2009IU.mL\u22121) in 224\/327 PWMHs (69%) and the median time with normalized FVIII was 3.9\u2009hours (0.0\u201354.1\u2009hours). Following the response profiles to DDAVP defined by the four efficacy scores, four groups of F8 variants were isolated, and then compared using survival curves with normalized FVIII (p\u2009&lt;\u20090.0001): \u201clong-lastingly effective\u201d [p.(Glu739Lys), p.(Ser2030Asn), p.(Arg2178His), p.(Gln2208Glu), and T-stretch deletion in intron 13]; \u201cmoderately effective\u201d [p.(Ser112Phe), p.(Ala219Thr), p.(Thr2105Ile), p.Phe2146Ser), and p.(Asp2150Asn)]; \u201cmoderately ineffective\u201d [p.Ala81Asp), p.(Gln324Pro), p.(Tyr492His), p.(Arg612Cys), p.(Met701Val), p.(Val2035Asn), and p.(Arg2178Cys)]; and \u201cfrequently ineffective\u201d [c.-219C\u2009&gt;\u2009T, p.(Cys2040Tyr), p.(Tyr2169His), p.(Pro2319Leu), and p.(Arg2326Gln)].<\/jats:p><jats:p>\n            Conclusion\u2003In view of our data, we propose indications for DDAVP use in PWMH based on F8 variants for minor and major invasive procedures.<\/jats:p>","DOI":"10.1055\/a-2329-3375","type":"journal-article","created":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T23:25:51Z","timestamp":1715988351000},"page":"922-936","source":"Crossref","is-referenced-by-count":4,"title":["Genotype-Dependent Response to Desmopressin in Hemophilia A and Proposal of a Predictive Response Score"],"prefix":"10.1055","volume":"124","clinical-trial-number":[{"clinical-trial-number":"nct05628558","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Beno\u00eet","family":"Guillet","sequence":"additional","affiliation":[{"name":"CRH, CRC-MHC (Centre de R\u00e9f\u00e9rence de l'H\u00e9mophilie, Centre de Ressource et de Comp\u00e9tence des Maladies H\u00e9morragiques Constitutionnelles), University Hospital, Rennes, France"},{"name":"Univ Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de Recherche en sant\u00e9, Environnement et Travail). UMR_S 1085, Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxime","family":"Pawlowski","sequence":"additional","affiliation":[{"name":"CRH, CRC-MHC (Centre de R\u00e9f\u00e9rence de l'H\u00e9mophilie, Centre de Ressource et de Comp\u00e9tence des Maladies H\u00e9morragiques Constitutionnelles), University Hospital, Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Boisseau","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9n\u00e9tique Mol\u00e9culaire, Service de G\u00e9n\u00e9tique M\u00e9dicale, CHU de Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohann","family":"R\u00e9pess\u00e9","sequence":"additional","affiliation":[{"name":"Haemophilia Treatment Center, University Hospital of Caen, Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Beurrier","sequence":"additional","affiliation":[{"name":"Haemophilia Treatment Center, University Hospital of Angers, Pays de la Loire, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Bayart","sequence":"additional","affiliation":[{"name":"CRH, CRC-MHC (Centre de R\u00e9f\u00e9rence de l'H\u00e9mophilie, Centre de Ressource et de Comp\u00e9tence des Maladies H\u00e9morragiques Constitutionnelles), University Hospital, Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7134-0713","authenticated-orcid":false,"given":"Xavier","family":"Delavenne","sequence":"additional","affiliation":[{"name":"INSERM, UMR 1059, Dysfonction Vasculaire et de l'H\u00e9mostase, Universit\u00e9 de Lyon, Saint Etienne, France"},{"name":"Laboratoire de Pharmacologie \u2013 Toxicologie, CHU de Saint-Etienne, Saint-Etienne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Trossa\u00ebrt","sequence":"additional","affiliation":[{"name":"Haemophilia Treatment Center, University Hospital of Nantes, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Lenting","sequence":"additional","affiliation":[{"name":"Laboratory for Hemostasis, Inflammation & Thrombosis, Unit\u00e9 Mixe de Recherche 1176, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Universit\u00e9 Paris-Saclay, 94276 Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2024,6,11]]},"reference":[{"issue":"03","key":"ref1","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1111\/j.1538-7836.2009.03717.x","article-title":"Mild hemophilia A","volume":"8","author":"M Franchini","year":"2010","journal-title":"J Thromb 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Castaman","year":"2009","journal-title":"J Thromb Haemost"},{"issue":"04","key":"ref14","doi-asserted-by":"crossref","first-page":"271","DOI":"10.5482\/HAMO-12-06-0012","article-title":"Desmopressin testing in haemophilia A patients and carriers: results of a multi centre survey","volume":"32","author":"R Kn\u00f6fler","year":"2012","journal-title":"Hamostaseologie"},{"issue":"03","key":"ref15","doi-asserted-by":"crossref","first-page":"550","DOI":"10.3324\/haematol.2017.180059","article-title":"Desmopressin in moderate hemophilia A patients: a treatment worth considering","volume":"103","author":"J I Loomans","year":"2018","journal-title":"Haematologica"},{"issue":"07","key":"ref16","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1002\/humu.20345","article-title":"Detection of 95 novel mutations in coagulation factor VIII gene F8 responsible for hemophilia A: results from a single institution","volume":"27","author":"B Guillet","year":"2006","journal-title":"Hum 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New insights into factor VIII-von Willebrand factor interactions","volume":"121","author":"M Jacquemin","year":"2009","journal-title":"Acta Haematol"},{"issue":"11","key":"ref26","doi-asserted-by":"crossref","first-page":"1954","DOI":"10.1182\/blood-2013-02-483263","article-title":"Factor VIII gene (F8) mutation and risk of inhibitor development in nonsevere hemophilia A","volume":"122","author":"C L Eckhardt","year":"2013","journal-title":"Blood"},{"issue":"03","key":"ref27","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1111\/j.1538-7836.2007.02861.x","article-title":"Mild hemophilia A with factor VIII assay discrepancy: using thrombin generation assay to assess the bleeding phenotype","volume":"6","author":"M Trossa\u00ebrt","year":"2008","journal-title":"J Thromb Haemost"}],"container-title":["Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2329-3375.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T12:17:30Z","timestamp":1730809050000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2329-3375"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,17]]},"references-count":27,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,9,27]]},"published-print":{"date-parts":[[2024,10]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2329-3375","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0340-6245","2567-689X"],"issn-type":[{"value":"0340-6245","type":"print"},{"value":"2567-689X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,5,17]]},"published":{"date-parts":[[2024,5,17]]}}}