A novel ELISA-based diagnosis of acquired von Willebrand disease with increased VWF proteolysis

Antoine Rauch; Claudine Caron; Flavien Vincent; Emmanuelle Jeanpierre; Catherine Ternisien; Pierre Boisseau; Christophe Zawadzki; Edith Fressinaud; Annie Borel-Derlon; Sylvie Hermoire; Camille Paris; Cécile Lavenu-Bombled; Agnès Veyradier; Alexandre Ung; André Vincentelli; Eric Van Belle; Peter J. Lenting; Jenny Goudemand; Sophie Susen

doi:10.1160/TH15-08-0638

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2016; 115(05): 950-959
DOI: 10.1160/TH15-08-0638

Coagulation and Fibrinolysis

Schattauer GmbH

A novel ELISA-based diagnosis of acquired von Willebrand disease with increased VWF proteolysis

Antoine Rauch

¹Département d'Hématologie Transfusion, CHU Lille, Lille, France

²INSERM UMR 1011, Univ Lille 2, Institut Pasteur de Lille, Lille, France

,

Claudine Caron

¹Département d'Hématologie Transfusion, CHU Lille, Lille, France

,

Flavien Vincent

²INSERM UMR 1011, Univ Lille 2, Institut Pasteur de Lille, Lille, France

³Département de Cardiologie, CHU Lille, Lille, France

,

Emmanuelle Jeanpierre

¹Département d'Hématologie Transfusion, CHU Lille, Lille, France

,

Catherine Ternisien

⁴Hématologie Biologique, CHU Nantes, Nantes, France

,

Pierre Boisseau

⁵Laboratoire de génétique moléculaire, CHU Nantes, Nantes, France

,

Christophe Zawadzki

¹Département d'Hématologie Transfusion, CHU Lille, Lille, France

²INSERM UMR 1011, Univ Lille 2, Institut Pasteur de Lille, Lille, France

,

Edith Fressinaud

¹Département d'Hématologie Transfusion, CHU Lille, Lille, France

,

Annie Borel-Derlon

⁶Hématologie Biologique, Hôpital de la côte de Nacre, CHU Caen, Caen, France

,

Sylvie Hermoire

¹Département d'Hématologie Transfusion, CHU Lille, Lille, France

,

Camille Paris

¹Département d'Hématologie Transfusion, CHU Lille, Lille, France

,

Cécile Lavenu-Bombled

⁷Hématologie Biologique, Hôpital Lariboisière, AP-HP, Paris, France

,

Agnès Veyradier

⁸Inserm, UMR_S 1176, Univ. Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France

,

Alexandre Ung

¹Département d'Hématologie Transfusion, CHU Lille, Lille, France

,

André Vincentelli

²INSERM UMR 1011, Univ Lille 2, Institut Pasteur de Lille, Lille, France

³Département de Cardiologie, CHU Lille, Lille, France

,

Eric Van Belle

²INSERM UMR 1011, Univ Lille 2, Institut Pasteur de Lille, Lille, France

³Département de Cardiologie, CHU Lille, Lille, France

,

Peter J. Lenting

⁹INSERM Unit 770, Le Kremlin-Bicetre, Val-de-Marne, France

,

Jenny Goudemand

¹Département d'Hématologie Transfusion, CHU Lille, Lille, France

²INSERM UMR 1011, Univ Lille 2, Institut Pasteur de Lille, Lille, France

,

Sophie Susen

¹Département d'Hématologie Transfusion, CHU Lille, Lille, France

²INSERM UMR 1011, Univ Lille 2, Institut Pasteur de Lille, Lille, France

› Institutsangaben

Abstract

Summary

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 speeddependent increase in VWF-proteolysis was assessed in the LVAD model whereas no proteolysis was observed in TTP-patients. In VWDpatients, 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 VWFproteolysis 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.

Supplementary Material to this article is available online at www.thrombosis-online.com.

Keywords

von Willebrand disease - acquired von Willebrand syndrome - proteolysis - aortic stenosis - circulatory support device

Volltext

Referenzen

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