Anti-Factor IX Antibodies Displaying FVIIIa-Like Activity.

One of the key events during hemostasis is the conversion of the zymogen factor X (FX) into its enzymatically active form FXa by the protease factor IXa (FIXa). FIXa assembles on a phospholipid surface together with its cofactor factor VIIIa (FVIIIa) which transforms FIXa from a very poor enzyme into a highly active protease. In order to mimic the stimulating effect of coagulation FVIIIa on FIXa, we identified a series of antibodies specific for FIX that exhibit FVIII-like activity. Upon binding to human FIXa these antibodies increased the turnover number (k_cat) of FIXa-catalysed FX activation approximately 10-fold. Procoagulant activity of these anti-FIXa antibodies could be detected in model systems containing purified proteins as well as in FVIII-depleted plasma and FVIII-inhibitor plasma. In plasma-assays contact activators and tissue factor were applied as a trigger, and the antibodies were effective in both cases. Our findings demonstrate that FVIII can be at least partially replaced by an antibody which might open up a new strategy for improving the treatment of hemophilia.