title: High shear dependent von Willebrand factor self-assembly fostered by platelet interaction and controlled by ADAMTS13.
abstract: BACKGROUND
  The paradigm of activation induced platelet aggregation has recently been refuted under blood flow conditions with shear rates exceeding 20,000s(-1). These lead to reversible rolling platelet aggregates, which were dependent on the presence of immobilized and soluble von Willebrand factor.
  
  
  METHODS
  In vitro experiments using direct fluorescence video-microscopy were performed in wall parallel and stagnation point flow chambers with shear rates raised from 20,000 to 50,000s(-1). Washed blood cell suspension containing recombinant von Willebrand factor (rVWF) was perfused over rVWF or collagen coated surfaces.
  
  
  RESULTS
  Here we show for the first time with the visualization of rVWF that not only colloid and polymer, i.e. platelets and VWF, form a composite, but that VWF itself is capable of entirely reversible self-assembly. On a collagen surface the platelet-VWF-conglomerates did not roll but VWF nets bound permanently to the collagen fibers and captured and immobilized platelets from the flow. Lowering the shear rate below the threshold of 20,000s(-1) no longer dissolved these deposits. Ultralarge multimer containing rVWF was most effective compared to normal sized rVWF. The presence of ADAMTS13 limited rolling aggregate and platelet-VWF-conglomerate formation to a time window of 7-8minutes. Changing wall parallel flow to stagnation point flow halved the required shear rate threshold.
  
  
  CONCLUSIONS
  We conclude that flow dynamics can trigger reversible von Willebrand factor self-assembly and platelet-VWF-conglomerate accrual, which are regulated by ADAMTS13 to a time span needed by coagulation to stabilize it, e.g. in case of vessel injury.
authors.affiliation: Department of Transfusion Medicine, Cell Therapeutics and Hemostasis, Medical Center of the University of Munich, Germany. Electronic address: thorsten.kragh@med.uni-muenchen.de.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Kragh
authors.affiliation: Department of Transfusion Medicine, Cell Therapeutics and Hemostasis, Medical Center of the University of Munich, Germany.
authors.forename: Marina
authors.initials: M
authors.lastname: Napoleone
authors.affiliation: Department of Biophysical Chemistry, University of Konstanz, Germany.
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Fallah
authors.affiliation: Baxter Innovations GmbH, Vienna, Austria.
authors.forename: Herbert
authors.initials: H
authors.lastname: Gritsch
authors.affiliation: Boston University, Department of Mechanical Engineering, Boston, MA, USA.
authors.forename: Matthias F
authors.initials: MF
authors.lastname: Schneider
authors.affiliation: Baxter Innovations GmbH, Vienna, Austria.
authors.forename: Armin J
authors.initials: AJ
authors.lastname: Reininger
mesh_terms: D051722:ADAM Proteins / Q000097:blood* / Q000378:metabolism*; D000071120:ADAMTS13 Protein; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008856:Microscopy, Fluorescence / Q000379:methods; D018715:Microscopy, Video / Q000379:methods; D010973:Platelet Adhesiveness / Q000187:drug effects / Q000502:physiology; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014841:von Willebrand Factor / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D011994:Recombinant Proteins; D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human
keywords: ADAMTS 13; Fluid high shear; Stagnation point flow; Ultralarge von Willebrand factor; VWF-platelet conglomerates; Wall parallel flow