Human von Willebrand factor (VWF) is a plasma glycoprotein that mediates shear-dependent platelet adhesion to subendothelium and platelet-platelet interactions . VWF is synthesized by endothelial cells as an ultralarge molecule (ULVWF) which may contain more than 40 subunits (up to 20,000 kDa). Upon secretion, the size of the ULVWF is reduced by a specific metalloprotease (ADAMTS-13) . ADAMTS-13 cleaves the Tyr842-Met843 peptide bond in the VWF A2 domain, generating smaller multimers and proteolysis fragments . Uncleaved ULVWF is hyperreactive in its capacity to bind to the platelet glycoprotein Ib-IX complex . Thus, downregulation of VWF multimeric size helps avoid unwanted platelet agglutination . Indeed, severely deficient ADAMTS-13 activity has been demonstrated in most patients with thrombotic thrombocytopenic purpura (TTP) , a disorder that is characterized by the occurrence of microvascular thrombi made up of platelet aggregates containing ULVWF . Little is known about the biological mechanisms that regulate ADAMTS-13 activity. An inverse relationship between ADAMTS-13 activity and VWF plasma levels was found by Mannucci et al. [8,9]. They investigated ADAMTS-13 in patients with type 3 von Willebrand disease (VWD) with undetectable VWF plasma levels and showed that activity was approximately one third higher than it was in healthy individuals with normal VWF. Infusion of desmopressin (DDAVP) in healthy volunteers resulted in a two- to threefold increase in VWF, and a 10-20% decrease in ADAMTS-13 activity, whereas following experimental administration of DDAVP to type 3 VWD patients, VWF was still undetectable, and ADAMTS-13 was unmodified. On the other hand, therapy with plasma concentrates in such patients resulted in a transient increase in VWF, along with a decrease in ADAMTS-13. Based on these findings, it was hypothesized that VWF levels regulate ADAMTS-13 . ADAMTS-13 has never been measured in a large series of patients with type 1 VWD. The VWF susceptibility to ADAMTS-13 proteolysis has been recently investigated in individuals with type 1 VWD, but only qualitative results were presented . We examined 62 type 1 patients whose ADAMTS-13 activity we assumed would range between that of normal individuals and that of type 3 VWD. Moreover, we intended to broaden our knowledge on ADAMTS-13 in VWD by investigating some patients with type 2 VWD, since ADAMTS-13 was reported to be within the normal range in a few patients with qualitative variants (6 patients with type 2M Vicenza and 4 patients with type 2A), although results have not been shown .
- von Willebrand disease
- von Willebrand factor
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine