Platelet-induced expression of FVIII efficacious even in the presence of high-titer anti-FVIII inhibitory antibodies. (A) Recombinant human FVIII normalizes the survival of FVIIInull mice subjected to tail-clip survival when plasma FVIII levels are ≥ 2 IU/dL (no platelet FVIII). Mice with 2 IU/dL were infused with anti-FVIII inhibitory antibodies and survival to tail-clip challenge determined. Anti-FVIII inhibitory plasma abrogated the effect of 2 IU/dL of plasma FVIII with a reduction in survival (100% survival reduced to 33%) at 2.5 BU and no survival with higher titers (25 BU and 250 BU). (B) 2bF8-transgenic mice with no plasma FVIII (whole-blood FVIII level corresponding to 1.23% of normal) had normal survival, even in the presence of high-titer anti-FVIII inhibitory antibodies (250 BU). (Used with permission, with full details provided in J Clin Invest. 2006;116:1974-1982)
