Epitope mapping of the von Willebrand factor subunit distinguishes fragments present in normal and type IIA von Willebrand disease from those generated by plasmin.
A small but consistent proportion of the von Willebrand factor (vWF) in normal plasma is composed of 189, 176, and 140 kD fragments cleaved from the 225 kD subunit. A monoclonal antibody map of vWF, based on the reactivity of individual antibodies with cyanogen bromide and tryptic fragments of known carboxy and/or amino termini, showed that in normal and IIA von Willebrand disease (vWD) plasmas the 140 kD fragment was derived from the amino-terminal region, whereas the 176 kD fragment was derived from the carboxy-terminal region of the subunit. In type IIA vWD, however, the fragments comprised a greater proportion of circulating vWF. In contrast, plasmin cleaved a 176 kD fragment from the amino terminus and a 145 kD fragment from the carboxy terminus of the subunit. Species similar to these plasmin-cleaved fragments were demonstrated in plasmas from four patients treated with fibrinolytic agents, but not in IIA vWD.
D000911:Antibodies, Monoclonal; D000939:Epitopes / Q000032:analysis*; D005341:Fibrinolysin / Q000378:metabolism*; D006801:Humans; D046911:Macromolecular Substances; D008970:Molecular Weight; D010446:Peptide Fragments / Q000032:analysis / Q000276:immunology; D014842:von Willebrand Diseases / Q000097:blood*; D014841:von Willebrand Factor / Q000032:analysis / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D046911:Macromolecular Substances; D010446:Peptide Fragments; D014841:von Willebrand Factor; D005341:Fibrinolysin