title: The presence of active von Willebrand factor under various pathological conditions.
abstract: OBJECTIVE
  To highlight mechanisms that regulate the balance between latent and active von Willebrand factor (VWF), and describe pathological conditions leading to increased levels of active VWF.
  
  
  RESULTS
  Levels of circulating active VWF are increased in von Willebrand disease type 2B, HELLP syndrome, malaria and antiphospholipid syndrome.
  
  
  CONCLUSIONS
  Freshly secreted VWF consists of ultra-large multimers that interact spontaneously with platelets at the endothelial cell surface. Proteolysis of ultra-large VWF by a member of the disintegrin and metalloprotease with thrombospondin motif family (ADAMTS13) reduces both multimeric size and accessibility of platelet-adhesion sites. The resulting VWF molecules circulate as inactive multimers, which regain their platelet-adhesion capacity upon binding to the subendothelial matrix, in particular under conditions of high shear. Unfortunately, mechanisms responsible for suppression of circulating plasma levels of active VWF are hampered in a number of pathological conditions, leading to VWF-platelet aggregates associated with thrombotic complications or thrombocytopenia. A recently developed assay allowed us to monitor the presence of circulating active VWF and we found that several diseases are characterized by increased levels. Further analysis provided insight into mechanisms contributing to the presence of active VWF, which revealed that beta2-glycoprotein I may act as a natural regulator of VWF-platelet interactions.
authors.affiliation: Laboratory for Thrombosis and Haemostasis, Department of Clinical Chemistry & Haematology, University Medical Center Utrecht, The Netherlands.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Groot
authors.forename: Philip G
authors.initials: PG
authors.lastname: de Groot
authors.forename: Rob
authors.initials: R
authors.lastname: Fijnheer
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Lenting
mesh_terms: D019281:Dimerization; D004198:Disease Susceptibility / Q000209:etiology; D006801:Humans; D010973:Platelet Adhesiveness / Q000502:physiology; D053482:beta 2-Glycoprotein I / Q000502:physiology*; D014841:von Willebrand Factor / Q000378:metabolism / Q000502:physiology*
chemical_list: D053482:beta 2-Glycoprotein I; D014841:von Willebrand Factor