FACTOR-VIII ABNORMALITY IN SEVERE VONWILLEBRANDS DISEASE

We attempted to characterize the small amounts of factor VIII-Related antigen detectable in the severe recessive form of von Willebrand's disease with newly developed radioimmunoprecipitin techniques and radiocrossed immunoelectrophoresis. Previous studies have failed to demonstrate factor VIII-Related antigen in most patients tested, even with the highly sensitive immunoradiometric assays. Using the newer techniques, we found antigen in the plasma of six of eight patients with severe von Willebrand's disease from different kindreds. Qualitative abnormalities of the trace quantities of factor VIII-Related antigen were demonstrated in five of the patients, with absence or relative decrease of the larger, less anodal forms. In addition, five distinct patterns were observed, each suggesting a different molecular abnormality. Heterozygous parents had normal to moderately decreased factor VIII-Related antigen, with normal crossed immunoelectrophoretic patterns. This study suggests that severe von Willebrand's disease is a heterogeneous syndrome with various underlying molecular defects. (N Engl J Med 301:1307–1310,1979) VON WILLEBRAND'S disease of the classic “autosomal-dominant” form is usually symptomatic in the heterozygous state. A less common but clinically more severe “recessive” form of the disorder is manifest when inherited from both parents. The heterozygous carrier parents and siblings of these patients are either completely asymptomatic or only mildly affected.1 2 3 4 5 Crossed immunoelectrophoretic analysis of factor VIII–related antigen (see Table 1 for terminology) has demonstrated abnormalities in some kindreds with the “autosomal-dominant” form. The identifiable heterozygotes of such kindreds, whether symptomatic or not, characteristically have the same abnormality of factor VIII–related antigen.4,6 7 8 Previous studies of the more severe, recessive form of Von. © 1979, Massachusetts Medical Society. All rights reserved.