Hemophilia A and B coagulation defects, which are caused by deficiencies of
Factor VIII and Factor IX, respectively, can be bypassed by administration
of recombinant Factor VIIa. However, the short half-life of recombinant Fa
ctor VIIa in vivo negates its routine clinical use. We report here an in vi
vo method for the continuous generation of Factor VIIa. The method depends
on the implantation of a porous chamber that contains Factor Xa or XIIa, an
d continuously generates Factor VIIa bypass activity from the subject's own
Factor VII, which enters the chamber by diffusion. Once inside, the Factor
VII is cleaved to Factor VIIa by the immobilized Factor Xa or XIIa. The ne
wly created Factor VIIa diffuses out of the chamber and back into the circu
lation, where it can bypass the deficient Factors VIII or IX, and enable co
agulation to occur. In vitro, this method generates sufficient Factor VIIa
to substantially correct Factor VIII-deficient plasma when assessed by the
classical aPTT coagulation assay. In vivo, a Factor XIIa peritoneal implant
generates bypass activity for up to one month when tested in rhesus monkey
s. Implantation of such a chamber in a patient with hemophilia A or B could
eventually provide a Viable alternative to replacement therapies using exo
genous coagulation factors.