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Factor VIII antigen is present in normal individuals in multiple molecular forms which can be separated according to size. The intermediate and larger forms preferentially bind to platelets in the presence of ristocetin. In order to evaluate the possibility that Factor VIII antigen forms of large size may be an artifact of in vitro aggregation, we have ultracentrifuged plasma on a 20% sucrose cushion at 37°C for 10 min at 254,000 xg (peak). The rate of clearing of Factor VIII antigen was compared to that of IgM, fibrinogen, IgG, α1-antitrypsin and the S rate calculated to be between 15 and 18. These results indicate that Factor VIII-related antigen forms of high S exist even when plasma is maintained at physiological temperature and analyzed with minimal delay, suggesting that these large molecular forms also exist as such in vivo.  Two types of von Willebrand’s disease (vWd) have been identified according to size of Factor VIII antigen forms present in plasma. In Type I all forms of Factor VIII antigen are present but are decreased in quantity. In Type II large forms are missing and smaller forms are present in normal or increased quantities. Factor VIII antigen was isolated from plasma of one patient with Type I and two patients with Type II vWd by counter Immunoelectrophoresis. The Factor VIII antigen was then reduced and electrophoresed on SDS-containing polyacrylamide gels. The presence of carbohydrate was evaluated by staining with perchloric acid-Schiff’s reagent (PAS). The 210,000 MW Factor VIII antigen subunit from each patient was PAS-positive. Though subtle changes in carbohydrate content or composition could not be evaluated by this technique, a total defect of glycosylation is unlikely in this small sample of vWd patients.

Multiple Molecular Forms of Factor VIII Antigen in Normal Individuals and Von Willebrand’s Disease Patients