von Willebrand factor proteolysis is deficient in classic, but not in bonemarrow transplantation-associated, thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) after bone marrow transplantation (BMT) differs from classic TTP in its clinical course and therapy, A chara cteristic of classic TTP is the inhibition of a plasma protease that specif ically cleaves von Willebrand factor (VWF), thus reducing its multimeric si ze. We investigated whether this protease was also inhibited in BMT-associa ted TTP. Plasma from patients with classic or BMT-associated TTP was incuba ted with recombinant VWF R834Q, a vWF mutant with enhanced sensitivity to t he protease. The proteolysis of vWF multimers was analyzed and quantified o n Western blot, Metalloprotease activity was strongly inhibited in the clas sic TTP patient group, However, metalloprotease activity wits normal In the BMT-associated TTP patient group. The difference in activity between the t wo patient groups was highly significant (P =.0016). The results indicate t hat the etiologies of classic and BMT-associated TTP are indeed different a nd provide an explanation for the lack of success of plasma exchange in BMT -associated TTP. (C) 1999 by The American Society of Hematology.