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. Here, F8 is linked to hemophilia.