Factor VIII functions as a cofactor for Factor IXa in a membrane-bound enzyme complex. Membrane binding accelerates the activity of the Factor VIIIa-Factor IXa complex approx. 100000-fold, and the major phospholipid-binding motif of Factor VIII is thought to be on the C2 domain. In the present study, we prepared an fVIII-C2 (Factor VIII C2 domain) construct from Escherichia coli, and confirmed ...

I NHIBITORS to factor VIII develop in approximately 1 5% of patients with hemophilia with an incidence of approximately 8 per 1,000 patient-years of observation.’ Clinically, these can be divided into high response inhibitors, which exhibit an anamnestic response after exposure to factor VIII, and low response inhibitors, which do not exhibit significant anamnesis.2 Because of their neutralizin...

Normal human plasma contains a complex of two proteins that are important in hemostasis and coagulation. The factor VIII procoagulant protein (antihemophilic factor) and the factor VIll-related protein (von Willebrand factor) are under separate genetic control, have distinct biochemical and immunologic properties, and have unique and essential T HE IMPORTANCE of factor VIII in hemostasis and bl...

Factor VIII circulates in noncovalent complex with von Willebrand factor (vWf). The topography of this complex was evaluated by fluorescence energy transfer using factor VIII subunits modified with N-(1-pyrenyl)maleimide (NPM; fluorescence donor) and vWf-derived fragments modified with 7-diethylamino-3-[4'-maleimidylphenyl]-4-methyl coumarin (CPM; fluorescence acceptor). Results from a previous...

...................................................................................................................iii LIST OF PUBLICATIONS..............................................................................................v ACKNOWLEDGEMENTS ............................................................................................vi ABBREVIATIONS........................................

An immunoadsorbent method has been developed for the direct analysis of normal and variant plasma factor VIII. Using this method, the molecular defect responsible for mild hemophilia A has been identified for a patient whose plasma factor VIII activity is 0.05 unit/ml, even though the factor VIII antigen content is 3.25 units/ml. Although the variant factor VIII has an apparently normal molecul...

A well-known complication of factor VIII replacement therapy in patients with hemophilia A is the development of inhibitory antibodies. Several studies have demonstrated the presence of a binding site for factor VIII inhibitors in the A3 domain. Six different human monoclonal single-chain variable domain antibody fragments (scFv) directed toward the A3-C1 domains of factor VIII have been isolat...

Infusions of factor VIII at 50-100 U/kg were administered "on demand" for bleeding episodes, or once weekly, in eight patients (aged 3-20 years) with hemophilia A and historically high titer inhibitors to factor VIII. Inhibitors were eliminated and immunologic tolerance to factor VIII occurred in five of the eight patients within 5-31 months. Four patients had minimal anamnestic responses upon ...

The clinical course and coagulation profile of a pregnant patient with variant von Willebrand's disease were followed from the second trimester through puerperium. The clinical course was characterized by a normal delivery and absence of abnormal bleeding or need for replacement therapy. The coagulation profile demonstrated an increase in factor VIII procoagulant activity, factor-VIII-related a...