{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T16:50:01Z","timestamp":1794502201510,"version":"4.9.1"},"reference-count":29,"publisher":"American Society of Hematology","issue":"16","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,10,16]]},"abstract":"<jats:sec>\n                  <jats:title>Abstract<\/jats:title>\n                  <jats:p>Desmopressin (DDAVP) is often administered to correct factor VIII (FVIII) levels in female hemophilia A carriers (HACs). However, the post-DDAVP FVIII pharmacokinetic profiles have been reported only in small series in HACs. Therefore, this study analyzed the post-DDAVP FVIII and von Willebrand factor (VWF) response in 361 HACs. A population pharmacokinetic\/pharmacodynamic model was developed to analyze the VWF and FVIII levels by taking into account the F8 gene variants (n = 143 [39.6%] with null; and n = 218 [60.4%] with non-null variants), demographic and laboratory covariates. The before\/after DDAVP mean basal, peak and recovery FVIII activity (FVIII:C) levels were 0.34 IU\/mL (0.08-0.65), 1.13 IU\/mL (0.19-2.69), and 2.85 IU\/mL (1.06-7.13), respectively. Peak FVIII:C was \u22650.5 IU\/mL in 95.6% (345\/361) and \u22650.8 IU\/mL in 78.7% (284\/361) of patients. The covariate analysis showed a poorer DDAVP FVIII:C response for null than non-null F8 variants: lower mean FVIII:C peak (1.04 vs 1.23 IU\/mL; P &amp;lt; 5 \u00d7 10\u20135) and patients percentage with normalized FVIII:C (91.6% vs 98.1%; P = .0068), higher mean FVIII:C clearance (5898.83 vs 2704.06 IU\/h; P = 1.58 \u00d7 10\u201315), lower mean FVIII:C area under the curve during the first 12 hours (AUC0-12h =7.73 vs 9.06 IU\/mL per hour; P &amp;lt; 5 \u00d7 10\u20136), and shorter mean time with FVIII:C \u22650.8 IU\/mL (1.9 vs 4.1 hours; P &amp;lt; 6 \u00d7 10\u20136). HAC with body weight &amp;lt;35 kg had lower peak FVIII:C, higher FVIII:C clearance, lower AUC0-12h, and shorter time with FVIII:C \u22650.8 IU\/mL than HAC with body weight 35 to 70 kg. In HACs, the post-DDAVP FVIII response is strongly influenced by the F8 genotype and body weight.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1182\/blood.2025029829","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T17:59:27Z","timestamp":1755885567000},"page":"1991-2004","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":6,"title":["<i>F8<\/i> gene variants influence the response to desmopressin in hemophilia A carriers"],"prefix":"10.1182","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2938-8013","authenticated-orcid":false,"given":"Beno\u00eet","family":"Guillet","sequence":"first","affiliation":[{"name":"1Centre de R\u00e9f\u00e9rence de l\u2019H\u00e9mophilie, Centre de Ressource et de Comp\u00e9tence des Maladies H\u00e9morragiques Constitutionnelles University Hospital, UMR_S 1085, Rennes, France"},{"name":"2Universit\u00e9 de Rennes, Centre Hospitalier Universitaire Rennes, INSERM, \u00c9cole des Hautes \u00c9tudes en Sant\u00e9 Publique, Institut de Recherche en Sant\u00e9, Environnement et Travail, UMR_S 1085, Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4843-7805","authenticated-orcid":false,"given":"Roseline","family":"d\u2019Oiron","sequence":"additional","affiliation":[{"name":"3Centre de R\u00e9f\u00e9rence de l\u2019H\u00e9mophilie et des Maladies H\u00e9morragiques Rares, H\u00f4pital Bic\u00eatre, Assistance Publique\u2013H\u00f4pitaux de Paris, Universit\u00e9 Paris-Saclay, Le Kremlin Bic\u00eatre, France"},{"name":"4Hematopoiesis and Immunotherapy, UMR_S1176, INSERM, Universit\u00e9 Paris-Saclay, Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4072-839X","authenticated-orcid":false,"given":"Marc","family":"Trossaert","sequence":"additional","affiliation":[{"name":"5Centre de R\u00e9f\u00e9rence maladie de Willebrand, Centre de Ressource et de Comp\u00e9tence des Maladies H\u00e9morragiques Constitutionnelles, H\u00f4tel-Dieu University Hospital, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9n\u00e9dicte","family":"Wibaut","sequence":"additional","affiliation":[{"name":"6Centre de R\u00e9f\u00e9rence maladie de Willebrand, Centre de Ressource et de Comp\u00e9tence des Maladies H\u00e9morragiques Constitutionnelles, University Hospital, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9853-2635","authenticated-orcid":false,"given":"Brigitte","family":"Pan-Petesch","sequence":"additional","affiliation":[{"name":"7Centre de Ressource et de Comp\u00e9tence des Maladies H\u00e9morragiques Constitutionnelles, Service H\u00e9matologie H\u00e9mostase Clinique, Morvan University Hospital, Brest, 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