Factor VIII activation by thrombin is the result of a proteolytic cleavage of the procoagulant component. These studies examine the effect of human antibody on this activation step in a solid phase immunoadsorbent assay system. Radiolabeled factor VIII antibody: factor VIII protein immune complexes were bound to agarose beads by mouse monoclonal antifactor VIII R:Ag antibody. The incubation of ...

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...

Coagulation is triggered during the onset of myocardial infarction, resulting in vascular occlusion. However, a causal role for individual haemostatic factors in the development of thrombotic occlusion is not established. Three cases (all relatively young women) are reported of raised factor VIII associated with myocardial infarction. Two patients presented acutely with myocardial infarction at...

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...

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...

We studied the activation of factor X by the intrinsic pathway of blood coagulation using a new assay of factor X activation. When factor X tritiated in its sialic acid residues is activated, activation can be measured by the release of tritiated activation peptide, and the initial rate of activation can be determined under varying conditions. In the presence of phospholipid and calcium ions, f...

A recent review article in Blood’ dealt with the advantage of using highly purified factor VI11 (F VIII) concentrates for the treatment of hemophilia. These products have a high specific activity of F VIIIC and, if properly treated, do not contain contaminating viruses. However, despite a relatively high purity, therapeutic concentrations of conventionally prepared F VI11 concentrates still hav...