Representative histopathologic findings at 2 weeks after joint bleeding challenge. (A,E) Wild-type (WT, hemostatically normal) mouse knee joint after needle puncture and IA NS injection; joint space is well maintained with normal 3- or 4-cell layer synovial lining and no synovial hypervascularity. (B,F) FIX ^−/− mouse joint after needle puncture and IA NS injection; gross blood is seen in the joint space (pink arrow), which is narrowed by synovial proliferation (black arrow) with areas of discoloration resulting from hemosiderin staining (green arrow). (C,G) FIX ^−/− mouse joint after IV recombinant hFIX 50 IU/kg followed by needle puncture and IA NS injection; hypervascularity (low-power view) and synovial thickening (> 8-10 cell layers, black arrow, high-power view) are present. (D,H) FIX ^−/− mouse joint after needle puncture with coincident IA injection of hFIX 25 IU/kg; joint space is well maintained with thin synovial lining (black arrow) and smooth cartilage. Top panel, original magnification ×40; bottom panel, original magnification ×200.