Inhibitory antibody formation is a major complication of factor VIII replacement therapy in patients with hemophilia A. To better understand the pathogenesis of this immunologic reaction, we evaluated the role of T-cell costimulatory signals for antifactor VIII antibody formation in a murine model of hemophilia A. Repeated intravenous injections of factor VIII in these factor VIII-deficient mic...

Inhibitory antibody formation is a major complication of factor VIII replacement therapy in patients with hemophilia A. To better understand the pathogenesis of this immunologic reaction, we evaluated the role of T-cell costimulatory signals for antifactor VIII antibody formation in a murine model of hemophilia A. Repeated intravenous injections of factor VIII in these factor VIII–deficient mic...

Recombinant blood clotting factor VIII is one of the most complex proteins for industrial manufacturing due to the low efficiency of its gene transcription, massive intracellular loss of its proprotein during post-translational processing, and the instability of the secreted protein. Improvement in hemophilia A therapy requires a steady increase in the production of factor VIII drugs despite ti...

A standard lyophilised triple cryoprecipitate preparation, stabilised by the addition of Synthamin 17, was heat treated at 60 degrees C for 48 hours. The total protein content, factor VIII concentration, and factor VIII recovery were not affected by the heat treatment procedure. Heat treatment did not influence the reconstitution characteristics of the freeze dried preparation and there were no...

Four years' experience with a method for preparing a high-purity, low-fibrinogen, heat-treated factor VIII concentrate is reported. The process, batch adsorption of a cryoprecipitate extract with controlled-pore glass granules, removes 77 percent of the cryoprecipitate fibrinogen, resulting in a final concentrate-specific activity of 0.74 IU factor VIII per mg of protein at a yield of 194 IU fa...

The interaction between human Factor VIII and immobilized multimeric von Willebrand Factor (vWF) was characterized. Equilibrium binding studies indicated the presence of multiple classes of Factor VIII-binding sites on vWF. The high-affinity binding (Kd = 2.1 x 10(-10) M) was restricted to only 1-2% of the vWF subunits. Competition studies with monoclonal antibodies with known epitopes demonstr...

Immunologic methods were employed in an attempt to identify a potent procoagulant present in homogenates of human skin fibroblasts cultured in vitro. The activity of this procoagulant was restricted to the early stages of coagulation and was heretofore considered to be due to tissue factor (tissue thromboplastin, factor Ill) either alone or in combination with one or more of the first-stage coa...

156. Cryopreservation of recombinant antihemophilic Factor VIII. Effect of biopolymers. Nelly M. Tsvetkova, Omkar Joshi, Arnaud Desponds, D.Q. Wang, Paul Wu, Bayer HealthCare LLC, Berkeley, CA, USA Recombinant Factor VIII, an essential coagulation factor in the blood, is one of the most complex proteins manufactured today. Currently the only therapy for hemophilia A is life-long administration ...