title: A novel ELISA-based diagnosis of acquired von Willebrand disease with increased VWF proteolysis.
abstract: Von Willebrand disease-type 2A (VWD-2A) and acquired von Willebrand syndrome (AVWS) due to aortic stenosis (AS) or left ventricular assist device (LVAD) are associated with an increased proteolysis of von Willebrand factor (VWF). Analysis of VWF multimeric profile is the most sensitive way to assess such increased VWF-proteolysis. However, several technical aspects hamper a large diffusion among routine diagnosis laboratories. This makes early diagnosis and early appropriate care of increased proteolysis challenging. In this context of unmet medical need, we developed a new ELISA aiming a quick, easy and reliable assessment of VWF-proteolysis. This ELISA was assessed successively in a LVAD-model, healthy subjects (n=39), acquired TTP-patients (n=4), VWD-patients (including VWD-2A(IIA), n=22; VWD-2B, n=26; VWD-2A(IIE), n=21; and VWD-1C, n=8) and in AVWS-patients (AS, n=9; LVAD, n=9; and MGUS, n=8). A standard of VWF-proteolysis was specifically developed. Extent of VWF-proteolysis was expressed as relative percentage and as VWF proteolysis/VWF:Ag ratio. A speed-dependent increase in VWF-proteolysis was assessed in the LVAD model whereas no proteolysis was observed in TTP-patients. In VWD-patients, VWF-proteolysis was significantly increased in VWD-2A(IIA) and VWD-2B and significantly decreased in VWD-2A(IIE) versus controls (p< 0.0001). In AVWS-patients, VWF-proteolysis was significantly increased in AS- and LVAD-patients compared to controls (p< 0.0001) and not detectable in MGUS-patients. A significant increase in VWF-proteolysis was detected as soon as three hours after LVAD implantation (p< 0.01). In conclusion, we describe a new ELISA allowing a rapid and accurate diagnosis of VWF-proteolysis validated in three different clinical situations. This assay represents a helpful alternative to electrophoresis-based assay in the diagnosis and management of AVWS with increased VWF-proteolysis.
authors.forename: Antoine
authors.initials: A
authors.lastname: Rauch
authors.forename: Claudine
authors.initials: C
authors.lastname: Caron
authors.forename: Flavien
authors.initials: F
authors.lastname: Vincent
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Jeanpierre
authors.forename: Catherine
authors.initials: C
authors.lastname: Ternisien
authors.forename: Pierre
authors.initials: P
authors.lastname: Boisseau
authors.forename: Christophe
authors.initials: C
authors.lastname: Zawadzki
authors.forename: Edith
authors.initials: E
authors.lastname: Fressinaud
authors.forename: Annie
authors.initials: A
authors.lastname: Borel-Derlon
authors.forename: Sylvie
authors.initials: S
authors.lastname: Hermoire
authors.forename: Camille
authors.initials: C
authors.lastname: Paris
authors.forename: Cécile
authors.initials: C
authors.lastname: Lavenu-Bombled
authors.forename: Agnès
authors.initials: A
authors.lastname: Veyradier
authors.forename: Alexandre
authors.initials: A
authors.lastname: Ung
authors.forename: André
authors.initials: A
authors.lastname: Vincentelli
authors.forename: Eric
authors.initials: E
authors.lastname: van Belle
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Lenting
authors.forename: Jenny
authors.initials: J
authors.lastname: Goudemand
authors.affiliation: Sophie Susen, Centre de Biologie Pathologie, Centre Hospitalier Régional, 59037 Lille Cedex, France, Tel.: +33 3 20 44 59 37, Fax:+33 3 20 44 69 89, E-mail: sophiesusen@aol.com.
authors.forename: Sophie
authors.initials: S
authors.lastname: Susen
mesh_terms: D019943:Amino Acid Substitution; D001024:Aortic Valve Stenosis / Q000150:complications; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D006353:Heart-Assist Devices / Q000009:adverse effects; D006801:Humans; D020125:Mutation, Missense; D055503:Protein Multimerization; D059748:Proteolysis; D056728:von Willebrand Disease, Type 2 / Q000097:blood / Q000175:diagnosis; D014842:von Willebrand Diseases / Q000097:blood* / Q000175:diagnosis* / Q000209:etiology; D014841:von Willebrand Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D014841:von Willebrand Factor
keywords: acquired von Willebrand syndrome; aortic stenosis; circulatory support device; proteolysis; von Willebrand disease