title: Continuous infusion of monoclonal antibody-purified factor VIII: rational approach to serious hemorrhage in patients with allo-/autoantibodies to factor VIII.
abstract: 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.
authors.affiliation: Division of Hematology/Oncology, Childrens Hospital of Los Angeles, CA 90027.
authors.forename: E M
authors.initials: EM
authors.lastname: Gordon
authors.forename: F
authors.initials: F
authors.lastname: al-Batniji
authors.forename: J C
authors.initials: JC
authors.lastname: Goldsmith
mesh_terms: D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D001323:Autoantibodies / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005169:Factor VIII / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000302:isolation & purification; D006470:Hemorrhage / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007262:Infusions, Intravenous; D007518:Isoantibodies / Q000097:blood; D007700:Kinetics; D008297:Male
chemical_list: D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007518:Isoantibodies; D005169:Factor VIII