Direct radioimmune detection in human plasma of the association between factor VIII procoagulant protein and von Willebrand factor, and the interaction of von Willebrand factor-bound procoagulant VIII with platelets.
The predominant procoagulant factor VIII (VIII:C) form in normal human plasma containing various combinations of anticoagulants and serine/cysteine protease inhibitors is a protein with mol wt 2.6 +/- 0.2 X 10(5). This protein can be detected by 125I-anti-VIII:C Fab binding and gel electrophoresis in the presence and absence of sodium dodecylsulfate (SDS) and is distinct from the subunit of factor VIII/von Willebrand factor (VIII:vWF) multimers. No larger VIII:C form is present in plasma from patients with severe congenital deficiencies of each of the coagulation factors, other than VIII:C. The mol wt approximately 2.6 X 10(5) VIII:C form is, therefore, likely to be the in vivo procoagulant form of VIII:C, rather than a partially proteolyzed, partially activated derivative of a larger precursor. About 60% of this procoagulant mol wt approximately 2.6 X 10(5) VIII:C form in plasma is present in noncovalent complexes with larger VIII:vWF multimers, which attach reversibly to platelet surfaces in the presence of ristocetin. This VIII:vWF-bound protein of mol wt approximately 2.6 X 10(5) may be the plasma procoagulant form of VIII:C which, after proteolytic activation, accelerates the IXa-mediated cleavage and activation of X postulated to occur on platelet surfaces.
D000941:Antigens / Q000032:analysis; D001777:Blood Coagulation; D001779:Blood Coagulation Factors / Q000502:physiology*; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology*; D004591:Electrophoresis, Polyacrylamide Gel; D005169:Factor VIII / Q000032:analysis / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007123:Immunoelectrophoresis, Two-Dimensional; D012310:Ristocetin / Q000378:metabolism; D012967:Sodium Dodecyl Sulfate; D014841:von Willebrand Factor / Q000378:metabolism / Q000502:physiology*
D000941:Antigens; D001779:Blood Coagulation Factors; D014841:von Willebrand Factor; D012310:Ristocetin; D012967:Sodium Dodecyl Sulfate; D005169:Factor VIII