Assessment of phenotypic correction. (A) Tail clip survival test assessed phenotypic correction of hemophilia A mice. All T2F8 transgenic mice survived tail clipping. (B) FeCl₃-induced thrombosis formation study. Four of 7 T2F8^tg+/− mice developed complete occlusion in the FeCl₃-induced carotid arterial injury model, which is not significantly different from WT controls (P = .41). (C) Electrical-induced femoral vein injury model. The volume of clot in T2F8^tg+/− mice is 23-fold higher than in FVIII^null mice (P < .05). (D) Tail clip survival test of hFVIII immunized T2F8 transgenic mice. T2F8 transgenic mice were immunized once with rhFVIII (with adjuvant) by intraperitoneal injection. Two weeks after immunization, plasma was used for inhibitor quantitation, and tail clip survival test was performed. Only 20% of T2F8^tg+/+ or T2F8^tg+/− animals survived tail clip challenge. No T2F8^TgVWF^−/− mice survived tail clipping in the presence of inhibitors. These results demonstrate that endothelial cell–derived FVIII restores hemostasis to hemophilia A mice, but has limited clinical efficacy in the presence of anti-FVIII inhibitory antibodies.