Structural Analysis of Factor VIII Antigen in Von Willebrand Disease

The Factor VIII antigen molecules in the plasma of patients with classical type 1 and variant type 2A von Willebrand disease were compared to the Factor VIII antigen molecules in normal plasma. Factor VIII antigen was isolated from plasma by solid-phase immunoprecipitation and analyzed by NaDodSO4/polyacrylamide gel electrophoresis; the stained Factor VIII antigen bands were removed, radioiodinated, and subjected to tryptic digestion. Computerized analysis of autoradiographs revealed that the two-dimensional peptide maps of the different Factor VIII antigens were remarkably similar. The results suggest that the Factor VIII antigen molecules in these two forms of von Willebrand disease are probably identical to the Factor VIII antigen molecules present in normal plasma. It is thus likely that the differences observed in plasma Factor VIII antigen in classical and variant von Willebrand disease are not due to qualitatively abnormal molecules but rather represent quantitative shifts in the metabolism of normal Factor VIII antigen molecules.