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N Engl J Med. 2007; 357: 535-544
and pharmacokinetic studies have found that, although increasing the time above factor levels of 1% substantially reduces bleeds, 2 Collins PW Blanchette VS Fischer K et al. Break-through bleeding in relation to predicted factor VIII levels in patients receiving prophylactic treatment for severe hemophilia A.J Thromb Haemost. 2009; 7: 413-420
maintaining levels of 15% eliminates bleeds. 3 den Uijl IE Fischer K Van Der Bom JG Grobbee DE Rosendaal FR Plug I Analysis of low frequency bleeding data: the association of joint bleeds according to baseline FVIII activity levels.Haemophilia. 2011; 17: 41-44
Because compliance is the best determinant of factor VIII and bleeding, 2 Collins PW Blanchette VS Fischer K et al. Break-through bleeding in relation to predicted factor VIII levels in patients receiving prophylactic treatment for severe hemophilia A.J Thromb Haemost. 2009; 7: 413-420
efforts to reduce dose frequency by improving half-life led to the development of extended half-life factor concentrate by Fc-fusion, albumin fusion, and pegylation technologies.
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