{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T11:45:21Z","timestamp":1770983121617,"version":"3.50.1"},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,3,15]],"date-time":"2005-03-15T00:00:00Z","timestamp":1110844800000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2005,3]]},"abstract":"<jats:p><jats:bold>Summary.\u2002<\/jats:bold>Recombinant activated factor VII (rFVIIa), licensed in 1999 for treatment of haemophilia patients with inhibitors (HI), represents an important advance in the therapeutic armamentarium. Standard bolus dosing ranges from 90 to 120\u2003mcg\u2003kg<jats:sup>\u22121<\/jats:sup>every 2\u20133\u2003h until arrest of bleeding. As licensure, clinical use of rFVIIa has increased and broadened. Clinicians now use a wide dose range, 90\u2013300\u2003mcg\u2003kg<jats:sup>\u22121<\/jats:sup>. High\u2010dose regimens may optimize thrombin generation or burst, and may allow for prolonged dose interval. The Hemophilia and Thrombosis Research Society (HTRS) maintains a registry database to study haemophilia treatment and related disorders, particularly treatment of acute bleeding in HI, acquired haemophilia, FVII deficiency and von Willebrand's disease (VWD). To assess the effect of rFVIIa dose on efficacy and safety in the treatment of acute bleeding in HI, data from the HTRS database from January 2000 through June 2002 were analysed. Bleeding episodes were grouped by bolus rFVIIa dose range: &lt;100, 100\u2013150, 150\u2013200 and &gt;200\u2003mcg\u2003kg<jats:sup>\u22121<\/jats:sup>. Investigator\u2010reported efficacy for the first 72\u2003h of treatment was evaluated. Thirty\u2010eight congenital HI patients were treated for 555 bleeding episodes. Patient age range was 1\u201355\u2003years (median: 14). Bleeding episodes were spontaneous (45%), caused by trauma (38%), or because of surgery, dental, diagnostic, or medical procedures (17%); bleeding occurred in joint, muscle, and intra\/extracranial sites. Treatment location included: 80% at home, 12% at other facilities (treatment centres, ER, inpatient and OR), and 8% at both home\/other facilities. Median total dose given over 72\u2003h was 360\u2003mcg\u2003kg<jats:sup>\u22121<\/jats:sup>(range: 40\u20134281, mean: 537). Bleeding stopped in 87% of the episodes. Bleeding cessation rate was 84% for the three lower dose groups, and 97% for the highest dose group (<jats:italic>P<\/jats:italic>\u2003&lt;\u20030.001). Five patients experienced nine adverse events (AEs). AE rates were &lt;1% for &lt;100, 5% for 100\u2013150, 0% for 150\u2013200, &lt;1% for &gt;200\u2003mcg\u2003kg<jats:sup>\u22121<\/jats:sup>dose group. Decreased therapeutic response accounted for eight of the nine AEs. These data, which represent the most comprehensive report of rFVIIa use since the USA licensure, demonstrate that bleeding episodes in HI patients can be treated safely and effectively at home and that doses up to 346\u2003mcg\u2003kg<jats:sup>\u22121<\/jats:sup>appear to be well\u2010tolerated. Additionally, rFVIIa doses &gt;200\u2003mcg\u2003kg<jats:sup>\u22121<\/jats:sup>appear to significantly increase efficacy (97% in the high\u2010dose group, compared with 84% in the lower dose groups). Optimal dosing remains to be determined; specifically, what the lowest effective dose is and whether a single high\u2010dose bolus eliminates the need for repeated dosing. Recombinant FVIIa appears to have a wide safety margin that may allow dose escalation to address these questions.<\/jats:p>","DOI":"10.1111\/j.1365-2516.2005.01075.x","type":"journal-article","created":{"date-parts":[[2005,3,15]],"date-time":"2005-03-15T11:13:19Z","timestamp":1110885199000},"page":"100-106","source":"Crossref","is-referenced-by-count":140,"title":["Dose effect and efficacy of rFVIIa in the treatment of haemophilia patients with inhibitors: analysis from the Hemophilia and Thrombosis Research Society Registry"],"prefix":"10.1111","volume":"11","author":[{"given":"R.","family":"Parameswaran","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. D.","family":"Shapiro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. C.","family":"Gill","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. 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