title: von Willebrand factor proteolysis is deficient in classic, but not in bone marrow transplantation-associated, thrombotic thrombocytopenic purpura.
abstract: Thrombotic thrombocytopenic purpura (TTP) after bone marrow transplantation (BMT) differs from classic TTP in its clinical course and therapy. A characteristic of classic TTP is the inhibition of a plasma protease that specifically cleaves von Willebrand factor (vWF), thus reducing its multimeric size. We investigated whether this protease was also inhibited in BMT-associated TTP. Plasma from patients with classic or BMT-associated TTP was incubated with recombinant vWF R834Q, a vWF mutant with enhanced sensitivity to the protease. The proteolysis of vWF multimers was analyzed and quantified on Western blot. Metalloprotease activity was strongly inhibited in the classic TTP patient group. However, metalloprotease activity was normal in the BMT-associated TTP patient group. The difference in activity between the two patient groups was highly significant (P =.0016). The results indicate that the etiologies of classic and BMT-associated TTP are indeed different and provide an explanation for the lack of success of plasma exchange in BMT-associated TTP.
authors.affiliation: Thrombosis and Haemostasis Laboratory, Department of Haematology, Institute of Biomembranes, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: R M
authors.initials: RM
authors.lastname: van der Plas
authors.forename: M E
authors.initials: ME
authors.lastname: Schiphorst
authors.forename: E G
authors.initials: EG
authors.lastname: Huizinga
authors.forename: R J
authors.initials: RJ
authors.lastname: Hené
authors.forename: L F
authors.initials: LF
authors.lastname: Verdonck
authors.forename: J J
authors.initials: JJ
authors.lastname: Sixma
authors.forename: R
authors.initials: R
authors.lastname: Fijnheer
mesh_terms: D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011697:Purpura, Thrombotic Thrombocytopenic / Q000097:blood* / Q000209:etiology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D014841:von Willebrand Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D011994:Recombinant Proteins; D014841:von Willebrand Factor