The Complex Multimeric Composition of Factor VIII/von Willebrand Factor

• Published in: Blood 1981-06, Vol.57 (6), p.1140-1143
• Main Authors: Ruggeri, Zaverio M., Zimmerman, Theodore S.
• Format: Article
• Language: English
• Subjects: Blood Coagulation Factors; Electrophoresis, Polyacrylamide Gel; Factor VIII; Humans; Immunoglobulin M; Molecular Weight; Polymers; von Willebrand Factor
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V57.6.1140.1140

We have analyzed the multimeric structure of factor VIII/von Willebrand factor in plasma by sodium dodecyl sulfate electrophoresis using gels of varying porosity and a discontinuous buffer system. Factor VIII/von Willebrand factor bands were identified by reaction with 125l-labeled affinity-purified antibody and subsequent autoradiography. In 1% agarose gels, normal plasma displayed a series of sharply defined oligomers. However, increasing the agarose concentration to 2.0% or utilizing mixtures of 0.8% agarose-1.75% acrylamide revealed two bands of lesser intensity interposed between the major bands. When the acrylamide concentration in the gels was increased to 2.5%, bands with a faster mobility than IgM and fibronectin were now evident. Type IIA von Willebrand’s disease showed not only an absence of the larger multimers but also a relative increase in several of the newly identified bands as compared to type IIB, type I, and normal. These studies suggest that factor VIII/von Willebrand factor in IIA von Willebrand’s disease is structurally different from that in other forms of the disorder. They also indicate that the multimeric composition of factor VIII/von Willebrand factor is more complex than can be explained by simple linear polymerization of a single protomer.