{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:25:12Z","timestamp":1778217912886,"version":"3.51.4"},"reference-count":26,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T00:00:00Z","timestamp":1456790400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Baxalta US, Inc."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>We previously showed that pharmacokinetic\u2010guided prophylaxis (<jats:styled-content style=\"fixed-case\">PKP<\/jats:styled-content>) allows the dosing interval to be extended while maintaining a specific trough level. However, the associations of peak factor VIII (<jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content>) levels and area under the curve (<jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content>) with breakthrough bleeding have not been investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>The aim of this study was to analyse data from the <jats:styled-content style=\"fixed-case\">PKP<\/jats:styled-content> arm to determine whether peak <jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content> levels, <jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content> and time with <jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content> levels in a haemostatically effective range are independent predictors of bleeding during prophylaxis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:italic>Post hoc<\/jats:italic> analysis of the association of <jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content> levels and <jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content> with annualized bleeding rate in 34 patients on <jats:styled-content style=\"fixed-case\">PKP<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>During 1 year of <jats:styled-content style=\"fixed-case\">PKP<\/jats:styled-content>, 131 bleeding episodes occurred in 24\/34 patients. Average peak <jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content> levels ranged from 24 to 168 IU dL<jats:sup>\u22121<\/jats:sup>, with higher values associated with a decreased risk for all bleeding (joint and non\u2010joint; <jats:italic>P<\/jats:italic> &lt; 0.01) and joint bleeding (<jats:italic>P<\/jats:italic> &lt; 0.01). Following <jats:styled-content style=\"fixed-case\">rFVIII<\/jats:styled-content> infusion, median percent of time spent with <jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content> levels &gt;20 IU dL<jats:sup>\u22121<\/jats:sup> was 22%; median <jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content> was 1363. Both values were significantly associated with a lower <jats:styled-content style=\"fixed-case\">ABR<\/jats:styled-content> when targeting a 1% trough at 72 h.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>When <jats:styled-content style=\"fixed-case\">PKP<\/jats:styled-content> was administered every third day, higher peak <jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content> levels, higher <jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content> and more time spent per week with <jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content> levels &gt;20 IU dL<jats:sup>\u22121<\/jats:sup> provided increased protection from joint and non\u2010joint bleeding. These data highlight the potential impact of variability in individual pharmacokinetic and bleeding risk and support the need for high peak levels and <jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content> in some patients treated every third day. The findings do not necessarily apply to alternate\u2010day or other prophylactic dosing regimens.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.12905","type":"journal-article","created":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T12:50:39Z","timestamp":1456836639000},"page":"514-520","source":"Crossref","is-referenced-by-count":61,"title":["Association of peak factor <scp>VIII<\/scp> levels and area under the curve with bleeding in patients with haemophilia A on every third day pharmacokinetic\u2010guided prophylaxis"],"prefix":"10.1111","volume":"22","author":[{"given":"L. A.","family":"Valentino","sequence":"first","affiliation":[{"name":"Baxalta US Inc. Deerfield IL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. W.","family":"Pipe","sequence":"additional","affiliation":[{"name":"University of Michigan Ann Arbor MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P. W.","family":"Collins","sequence":"additional","affiliation":[{"name":"School of Medicine Cardiff University Cardiff UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V. S.","family":"Blanchette","sequence":"additional","affiliation":[{"name":"Hospital for Sick Children Toronto ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Berntorp","sequence":"additional","affiliation":[{"name":"Lund University Skane University Hospital Malm\u00f6 Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Fischer","sequence":"additional","affiliation":[{"name":"Van Creveldkliniek University Medical Center Utrecht Utrecht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B. 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