The effect of VWF on plasma FVIII. (A) The level of FVIII:C is significantly decreased in T2F8^tg+/−VWF^+/− mice (P < .01) and was undetectable in T2F8^TgVWF^−/− mice. Approximately 10% of normal murine FVIII:C persisted in the plasma of VWF^−/− mice. (B) Murine plasma-derived VWF was infused into T2F8^TgVWF^−/− mice to restore VWF levels to approximately 25% of normal. (C) Endothelial cell–derived plasma FVIII was rescued by the infused VWF. These results demonstrate that survival of endothelial cell–derived plasma hFVIII is VWF-dependent.