Hemorrhage in a patient with
factor VIII inhibitor is associated with increased morbidity and mortality. Treatment with
factor IX complex concentrates or
recombinant factor VIIa (rVIIa) may not control
bleeding and may induce
thrombosis. In this study, continuous infusion of a
monoclonal antibody-purified
factor VIII [correction of
factor VII] concentrate (
Monoclate-P) was used successfully in two hemophilic patients with
factor VIII alloantibodies and one nonhemophilic patient with
a factor VIII
autoantibody. In two patients,
hemorrhage was life-threatening, and, in one,
bleeding did not stop with repeated infusions of
activated factor IX complex concentrates. The patients' ages ranged from 4 to 15 years, and the inhibitor levels from 6 to 300 Bethesda units/ml. Clinical hemostasis was excellent, and in vivo recovery of infused
factor VIII was achieved. When an excess of monoclonal
factor VIII was added to the inhibitor plasma in vitro, a stable level of residual
factor VIII activity was noted after an initial rapid loss. This second-order reaction occurs in plasmas of patients with type I
factor VIII inhibitors. In one patient, we showed that the saturation dose of the
factor VIII inhibitor predicted in vivo recovery of
factor VIII:C. These data emphasize the importance of characterizing the kinetic reactions of the
factor VIII inhibitor. Furthermore, we confirm previous reports that continuous infusion of monoclonal
factor VIII is a safe and effective treatment of patients with
factor VIII inhibitors in whom
hemorrhage is either life-threatening or refractory to standard treatment.