ABSTRACT
-The development of factor VIII and factor IX concentrates markedly improved the management
of hemophilia A and B and made home therapy possible. However, treatment of hemophilic
patients with acquired inhibitors remained difficult. The preparation of prothrombin
complex concentrates, nonactivated or activated, addressed this difficult clinical
problem, but their use was associated with serious side effects. Factor VIIa was found
to be a safer treatment modality. Factor VIIa per se is inactive and needs tissue
factor (TF) to become biologically active. TF serves as the receptor for factor VIIa.
TF is expressed from vessel walls only upon injury. Treatment of inhibitor patients
with plasma-derived factor VII was found to be successful. This led to the development
of recombinant factor VIIa, which was also found to be successful in managing hemophilia
patients with inhibitors. Up to this point, large numbers of patients have been treated
and few serious side effects have been noted. Because of its unique effects on the
hemostasis system, recombinant factor VIIa will be useful for other indications as
well, including patients with congenital factor VII deficiency, patients with bleeding
and liver function impairment, patients with quantitative and qualitative platelet
defects, and individuals who have sustained multiple trauma. The development of recombinant
factor VII is reviewed in detail.
KEYWORD
Hemophilia A - inhibitor - factor VII - recombinant factor VIIa - tissue factor
