title: Acquired von Willebrand factor deficiency caused by LVAD is ADAMTS-13 and platelet dependent.
abstract: BACKGROUND
  The high shear rates induced by left ventricular assist devices cause acquired von Willebrand disease (aVWD). We hypothesised that an ex vivo model could be established to study whether mechanical shear stress alone causes aVWD or whether this process depends also on the VWF cleavage protein ADAMTS-13 and on platelets.
  
  
  METHODS
  Healthy volunteers and two patients with congenital ADAMTS-13 deficiency donated blood. In vitro closed extracorporeal circuits were established using medically approved left ventricular assist devices (LVAD). VWF multimers were quantified by gel electrophoresis; VWF antigen, ristocetin cofactor activity (VWF:RCo), ADAMTS-13 levels and platelet function were assessed.
  
  
  RESULTS
  The high shear stress in the extracorporeal circulation rapidly decreased VWF:RCo and thereby the VWF:RCo/VWF:Ag ratio by 47% (p<0.01) to pathologically low values. Concomitantly, high molecular weight multimers (HMWM) decreased: up to 14-15 mers were visible on the gels at baseline, which were reduced by a maximum of 6-7 mers, corresponding to an average 68% lower densitometry signal of HMWM (p<0.001). This was accompanied by marked reduction of aggregation by various agonists (p<0.005). In contrast, the two patients with congenital thrombocytopenic purpura with virtually complete deficiency of ADAMTS-13 activity had only a minimal or no decrease in multimers (p<0.005 vs. healthy controls). Similarly, no or minimal depletion of large multimers occurred, when normal plasma circulated without platelets.
  
  
  CONCLUSIONS
  An in vitro model for LVAD associated aVWD demonstrated that ADAMTS-13 and platelets contribute to the depletion of HMWM of VWF.
authors.affiliation: Department of Laboratory Medicine, Division of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Austria.
authors.forename: Petra
authors.initials: P
authors.lastname: Jilma-Stohlawetz
authors.affiliation: Department of Laboratory Medicine, Division of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Quehenberger
authors.affiliation: Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Austria.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Schima
authors.affiliation: Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Stoiber
authors.affiliation: Department of Internal Medicine I, Division of Haematology and Haemostasis, Medical University of Vienna, Austria.
authors.forename: Paul
authors.initials: P
authors.lastname: Knöbl
authors.affiliation: Division of Cardiothoracic and Vascular Anesthesia, Medical University of Vienna, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Steinlechner
authors.affiliation: Division of Cardiothoracic and Vascular Anesthesia, Medical University of Vienna, Austria.
authors.forename: Alessia
authors.initials: A
authors.lastname: Felli
authors.affiliation: Clinical Pharmacology, Medical University of Vienna, Austria. Electronic address: Bernd.Jilma@meduniwien.ac.at.
authors.forename: Bernd
authors.initials: B
authors.lastname: Jilma
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism*; D000071120:ADAMTS13 Protein; D000293:Adolescent; D000328:Adult; D001792:Blood Platelets / Q000378:metabolism*; D005260:Female; D006353:Heart-Assist Devices / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult; D014842:von Willebrand Diseases / Q000209:etiology* / Q000378:metabolism*; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human
keywords: Circulatory support device; LVAD; Platelets