Some More Thoughts on Factor VIII Mimetics

I have previously posted some thoughts on factor VIII mimetics which mimic factor VIII function in supporting the activation of factor X by a mechanism not involving factor VIIa/tissue factor.  The function of factor in blood coagulation is a carefully orchestrated process involving (1) the generation of an active factor VIII from a partially active precursor protein,(2) activation of a blood platelet providing an environment for the association of enzyme (factor IXa), a substrate (factor X), and a cofactor, factor VIII, and (3) a mechanism to shut down the activity of factor VIII (activated protein C; dissociation of the factor VIIIa heterotrimer). So it would follow that the only material that would be useful in the treatment of hemophilia A is factor VIII or a derivative of factor VIII such as a factor VIII fusion protein with Fc and factor VIII mimetics would be useful in certain situations such as factor VIII inhibitors.  The reader is directed to a paper by Professor Pier Mannucci and others addressing this issue in greater detail.

Mannucci, P.M., Mancuso, M.E., Ssantagostino, E., and Franchini, M., Innovative pharmacological therapies for hemophilias not based on  deficient factor replacement, Semin.Thromb.Hemost., in press, 2016.