Factor VIII coagulant activity (VIII(C)) and the von Willebrand's disease antigen (Factor VIII-like antigen, vW-Ag) are biologically linked, and it has been suggested that they reside on the same molecule. However, insolubilized human isoantibody to VIII(C) and rabbit antiserum containing antibodies to VIII(C) and vW-Ag differentially bind and remove these entities from plasma, thus physically ...

Generation of coagulation factor Xa by the intrinsic pathway protease complex is essential for normal activation of the coagulation cascade in vivo. Monocytes and platelets provide membrane sites for assembly of components of this protease complex, factors IXa and VIII. Under biologically relevant conditions, expression of functional activity by this complex is associated with activation of fac...

Approximately 25% of patients with hemophilia A develop inhibitory antibodies after treatment with factor VIII. Most of the inhibitory activity is directed against epitopes in the A2 and C2 domains. Anti-A2 inhibitory antibodies recognize a 25-residue segment bounded by R484-I508. Several antigenic residues in this segment have been identified, including R484, R489, and P492. The immunogenicity...

To study the interrelationships of the major human coagulation pathways, factor X activation in normal and various deficient human plasmas was evaluated when clotting was triggered by dilute rabbit or human thromboplastin. Various dilutions of thromboplastin were added to plasma samples containing 3H-labeled factor X, and the time course of factor X activation was determined. At a 1/250 dilutio...

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 VIII-related protein (von Willebrand factor) are under separate genetic control, have distinct biochemical properties, and have unique and essential physiologic properties. While the nature of their interaction and t...

Affinity chromatography of human cryosupernatants on anti-human factor VIII-Sepharose yielded a plasma devoid of detectable factor VIIIC, VIIIR:Ag, and VIIIR:WF activities. This plasma was indistinguishable from severe congenital hemophilic plasma when used as substrate in factor VIII coagulant assays.

Thrombin causes an increase in factor VIII coagulant (VIII:C) activity, which is followed by a decay of VIII:C activity to below baseline levels. It has been suggested that a similar interaction of trace amounts of thrombin and factor VIII is a necessary prerequisite before factor VIII can participate in the coagulation cascade. In the current study, factor IXa, a serine protease with structura...