title: Extravascular FIX and coagulation.
abstract: This review summarizes the evidence that collagen IV binding is physiologically important, and that the extravascular compartment of FIX is composed of type IV collagen. As we have previously demonstrated, 7 days post-infusion, FIXWT(BeneFIX) is able to control bleeding as well as the same dosage of Alprolix in hemophilia B mice, tested using the saphenous vein bleeding model (Alprolix is a chimeric FIX molecule joined at its C terminus to a Fc domain). Furthermore, we have shown that in hemophilia B mice, doses of BeneFIX or Alprolix (up to a dose of 150 IU/kg) have increased bleeding-control effectiveness in proportion to the dose up to a certain limit: higher doses are no more effective than the 150 IU/kg dose. These studies suggest that in hemophilia B mice, tested using the saphenous vein bleeding model, three things are true: first, extravascular FIX is at least as important for coagulation as is circulating FIX; second, measuring circulating levels of FIX may not be the best criterion for designing new "longer lasting" FIX molecules; and third, trough levels are less diagnostic for FIX therapy than they are for FVIII therapy.
authors.affiliation: Biology and Pathology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3280 USA.
authors.forename: Darrel W
authors.initials: DW
authors.lastname: Stafford
keywords: Coagulation; Collagen IV; FIX; Hemophilia B