Human factor VIII/von Willebrand protein is a population of multimers which vary in
size but contain apparently identical subunits. Large-molecular-weight forms possess
higher ristocetin cofactor/von Willebrand activity than the native smaller oligomers.
Disulfide reduction of large factor VIII multimers results in progressively decreasing
molecular size and a loss of ristocetin cofactor activity. Small molecular forms of
factor VIII were adsorbed onto gold granules (average diameter 20-30 nm) and thereby
increased their ristocetin cofactor activity. The amount of adsorbed material and
the extent of activation were dependent on the pH of the colloid suspension. The maximum
recovery of von Willebrand activity was observed at pH 4.75. Aggregation of fixed
human platelets by factor VIII-coated gold particles was dependent on ristocetin concentration
and was not competitively inhibited by unbound low-molecular-weight factor VIII. These
results suggest that the subunits of the native small factor VIII species possess
potential binding affinity for platelet receptors, which is manifested following formation
of large factor VIII polymers. We conclude that an optimal size of remarkably high
molecular weight is required for efficient aggregation of platelets by factor VIII
as occurs during the primary phase of hemostasis.
Keywords
Factor VIII/von Willebrand factor - Platelet aggregation - Gold granules
