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

• Published in: Blood 1983-06, Vol.61 (6), p.1163-1173
• Main Authors: Moake, Joel L., Weinstein, Mark J., Troll, Joseph H., Chute, Leslie E., Colannino, Noreen M.
• Format: Article
• Language: English
• Subjects: Antigens - analysis; Blood Coagulation; Blood Coagulation Factors - physiology; Blood Platelets - metabolism; Blood Platelets - physiology; Electrophoresis, Polyacrylamide Gel; Factor VIII - analysis; Factor VIII - immunology; Factor VIII - metabolism; Factor VIII - physiology; Humans; Immunoelectrophoresis, Two-Dimensional; Ristocetin - metabolism; Sodium Dodecyl Sulfate; von Willebrand Factor - metabolism; von Willebrand Factor - physiology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V61.6.1163.1163

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 × 106. 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 (VllI: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 ~2.6 × 105 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 ~2.6 × 106 VIIIrC 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 ~2.6 × 105 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.