Variant forms of procoagulant-like factor VIII in hemophiliacs

Plasmas from two cross-reactive material (CRM) negative and two CRM positive hemophiliacs are shown to contain a biologically inactive procoagulant-like protein which is analogous to the low molecular weight active protein dissociated from the Factor VIII of normal individuals at high ionic strength. This low molecular weight protein (LMW) from the hemophiliacs elutes from column chromatography with a pattern similar to the normal. However, following polyacrylamide gel electrophoresis (PAGE) or isoelectric focusing (IEF), the protein bands, as demonstrated by Coomassie staining of reaction with antibody, show a striking picture of heterogeneity. Further biochemical characterization and comparison with LMW from normal individuals indicates that the hemophilic LMW protein has a wide variation in carbohydrate content ranging from approximately 12%, as is the case with the normal, to 39.5%. The data suggests that, like von Willebrand's disease, hemophilia may exist in variant forms with alteration in carbohydrate content responsible for differences in reactivity with antibody and possibly for lack of procoagulant activity.