Platelets Treated with Ticlopidine Are Less Reactive to Unusually Large von Willebrand Factor Multimers than Are Those Treated with Aspirin under High Shear Stress

2005 ◽  
Vol 34 (1) ◽  
pp. 35-40 ◽  
Author(s):  
M. Matsumoto ◽  
S. Kawaguchi ◽  
H. Ishizashi ◽  
H. Yagi ◽  
J. Iida ◽  
...  
Keyword(s):  
Shear Stress ◽  
Von Willebrand Factor ◽  
High Shear ◽  
High Shear Stress ◽  
Von Willebrand ◽  
Willebrand Factor

von Willebrand Factor Ristocetin Cofactor Activity Correlates with Platelet Function in a High Shear Stress System

2000 ◽  
Vol 84 (10) ◽  
pp. 727-728 ◽  
Author(s):  
Agnès Veyradier ◽  
Edith Fressinaud ◽  
Catherine Boyer-Neumann ◽  
Marc Trossaert ◽  
Dominique Meyer
Keyword(s):  
Shear Stress ◽  
Von Willebrand Factor ◽  
Stress System ◽  
High Shear ◽  
High Shear Stress ◽  
Cofactor Activity ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Ristocetin Cofactor ◽  
Ristocetin Cofactor Activity

scholarly journals Platelet adhesion involves a novel interaction between vimentin and von Willebrand factor under high shear stress

Blood ◽  
2014 ◽  
Vol 123 (17) ◽  
pp. 2715-2721 ◽  
Author(s):  
Qi Da ◽  
Molly Behymer ◽  
Juliana I. Correa ◽  
K. Vinod Vijayan ◽  
Miguel A. Cruz
Keyword(s):  
Shear Stress ◽  
Von Willebrand Factor ◽  
Platelet Adhesion ◽  
High Shear ◽  
High Shear Stress ◽  
Platelet Surface ◽  
Key Points ◽  
Von Willebrand ◽  
Willebrand Factor

Key Points Vimentin expressed on the platelet surface serves as adhesive receptor for VWF.

High Shear Stress and Immobilization of Von Willebrand Factor Promotes the VWF-Cleaving Protease Activity as Assessed by the Cone and Plate(let) Analyzer.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 849-849
Author(s):  
David Varon ◽  
Boris Shenkman ◽  
Ulrich Budde ◽  
Dorothea Angerhaus ◽  
Reinhard Schneppenheim ◽  
...  
Keyword(s):  
Shear Stress ◽  
Von Willebrand Factor ◽  
Platelet Adhesion ◽  
Thrombus Formation ◽  
Static Condition ◽  
High Shear ◽  
High Shear Stress ◽  
Polystyrene Surface ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract The metalloprotease ADAMTS-13 cleaves von Willebrand factor (VWF) that is released from endothelial cells as a large multimeric protein. However, the specific physiological conditions required for the function of this von Willebrand factor-cleaving protease (VWF-CP) are not yet established. In this study we determined the optimal conditions for the VWF-CP activity using the Cone and Plate(let) Analyzer (CPA). Proteolysis of a soluble recombinant VWF by a recombinant VWF-CP in the absence or the presence of BaCl2 (for induction of VWF-CP) was performed under static and flow (2050 s−1) conditions. The resulted fragments of the soluble VWF were immobilized on a polystyrene surface and non-adhering sites were blocked with 1% BSA. In parallel, polystyrene surface immobilized VWF was similarly treated by VWF-CP. The immobilized cleaved VWF fragments by the above protocols served as a substrate for citrated whole blood platelet adhesion under flow (2050 s−1). Reduction of platelet adhesion (surface coverage, SC) in BaCl2 treated compared to untrerated sample reflects the degree of VWF-CP activity. Platelet adhesion (SC, %) to VWF proteolytic products generated under the indicated conditions: Static w/o BaCl2 Static + BaCl2 Flow w/o BaCl2 Flow + BaCl2 Soluble VWF 15.0 ± 3.4 11.1 ± 2.7 13.6 ± 2.2 8.0 ± 2.1 Immobil. VWF 19.1 ± 3.0 12.0 ± 4.1 6.5 ± 1.1 1.0 ± 0.6 Maximal VWF-CP activity as reflected by maximal reduction (85%) of platelet adhesion was observed when immobilized VWF was treated by VWF-CP under flow. Minimal effect of VWF-CP activity was observed when soluble VWF was treated under static condition (26% reduction). Intermediate effect was observed with soluble VWF under flow (41%) and with immobilized VWF under static condition (37%). It should be noted that in the case of immobilized VWF application of flow alone (without BaCl2) was sufficient to induce a remarkable decrease of platelet adhesion (66%). In conclusion, both immobilization of VWF and high shear stress are important conditions for VWF-CP function, suggesting that stretching of immobilized VWF under flow exposes the VWF-cleavage site and thereby may serve as a control mechanism of platelet adhesion at the site of thrombus formation.

scholarly journals Total inhibition of high shear stress induced platelet aggregation by homodimeric von Willebrand factor A1-loop fragments

1999 ◽  
Vol 105 (4) ◽  
pp. 1092-1100 ◽  
Author(s):  
Shuji Miura ◽  
Yoshihiko Sakurai ◽  
Hideo Takatsuka ◽  
Akira Yoshioka ◽  
Masanori Matsumoto ◽  
...  
Keyword(s):  
Shear Stress ◽  
Platelet Aggregation ◽  
Von Willebrand Factor ◽  
High Shear ◽  
High Shear Stress ◽  
Total Inhibition ◽  
Von Willebrand ◽  
Willebrand Factor

The Platelet Glycoprotein Ib-von Willebrand Factor Interaction Activates the Collagen Receptor α2β1 and the Two Adhesive Receptors then Collaborate to Fully Activate Platelets to Form Thrombi.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1556-1556
Author(s):  
Junmei Chen ◽  
Jody L. Whitelock ◽  
Lisa D. Morales ◽  
Jose A. Lopez ◽  
Miguel A. Cruz
Keyword(s):  
Shear Stress ◽  
Von Willebrand Factor ◽  
Platelet Adhesion ◽  
Thrombus Formation ◽  
Platelet Glycoprotein ◽  
Type I ◽  
High Shear ◽  
High Shear Stress ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Integrin α2β1 (GP Ia/IIa) is a major platelet receptor for collagen, containing its collagen binding site within the α2 I domain. α2β1 changes conformation upon platelet activation, increasing its affinity for collagen. The conformational changes are reflected in the markedly different crystal structures obtained for the α2 I domain depending on whether it is free or bound to a collagen peptide. However, it is not known whether in flowing blood α2β1 on platelets is activated before binding to collagen. To address this issue, we identified an antibody that has higher affinity for the activated α2β1. We found that two antibodies that bind within the α2 I domain, 12F1 and 6F1, bound preferentially to ADP-activated platelets, with 12F1 displaying the most marked increase in binding with activation. We corroborated this result for 12F1 by showing that it binds with higher affinity to a gain-of-function I domain mutant than to either the wild-type I domain or to a loss-of-function mutant. In addition, when whole blood was perfused over a surface coated with 12F1, the antibody did not support the adhesion of unstimulated platelets. Because thrombus formation on collagen at a high shear stress is initiated by the binding of the platelet glycoprotein Ib-IX-V complex (GP Ib) to von Willebrand factor (VWF), we tested whether this interaction can activate α2β1, using 12F1 as a probe for integrin activation. We perfused blood over a surface coated with a mixture of VWF A1 domain (a GP Ib ligand) and 12F1, or VWF A1 and mouse IgG. Platelets rolled and did not attach stably on the A1/IgG surface, but they firmly bound and covered the A1/12F1 surface. The fact that 12F1 alone failed to capture resting platelets under flow but supported firm platelet adhesion if GP Ib interacted with VWF A1 strongly suggests that GP Ib ligation by VWF induces signals that activate α2β1 and increase its affinity for collagen. The two receptors (GP Ib and α2β1) then cooperate in platelet adhesion to collagen, which was demonstrated by perfusing, at a high shear stress, reconstituted blood lacking VWF and fibrinogen over surfaces coated with collagen or A1/collagen. The A1/collagen surface contained more firmly adherent platelets than the collagen surface; firm adhesion was blocked by 6F1. We then tested whether the signals from GP Ib and α2β1 cooperate to fully activate platelets and allow thrombus growth. For this, we perfused whole blood over a mixed matrix of A1 and the α2β1-specific type I collagen-derived triple-helical peptide, CP10. We observed that platelets not only firmly adhered to this surface, they also formed thrombi, similar to those seen on collagen surfaces. Thrombus formation was inhibited by either the αIIbβ3 antibodies or blocking the A1/CP10 surface with the recombinant α2 I domain. Together, our data indicate that platelets adhere to collagen in a stepwise fashion, beginning with the interaction of GP Ib with VWF, which rapidly activates α2β1 to engage collagen. The combination of adhesive ligand-receptor interactions induces the activation of integrin αIIbβ3, which enables thrombus formation.

Formation of Procoagulant Platelet Derived Microparticles through Platelet GPIb-Interaction with Von Willebrand Factor under High Shear Stress.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 414-414
Author(s):  
Armin J. Reininger ◽  
Harry F.G. Heijnen ◽  
Hannah Schumann ◽  
Wolfgang Schramm ◽  
Zaverio M. Ruggeri
Keyword(s):  
Shear Stress ◽  
Von Willebrand Factor ◽  
High Shear ◽  
High Shear Stress ◽  
Shear Rates ◽  
Tissue Factors ◽  
Membrane Tethers ◽  
Microparticle Formation ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract We describe here novel findings of the mechanism of initial platelet contact with immobilized von Willebrand factor (VWF) under high shear stress and how this leads to the formation of procoagulant platelet derived microparticles. In a parallel plate perfusion chamber whole blood was perfused over multimeric VWF or dimeric VWF A1 domain at shear rates between 2,000 s−1 and 40,000 s−1. Platelet attachment to VWF always occurred through glycoprotein Ibα receptors located in discrete adhesion points (DAPs), i.e. few limited membrane areas of 0.05 to 0.1 μm2 that arrested the platelets on the surface. The ongoing flow translocated such anchored platelets downstream, thus pulling membrane tethers from the intact and unstimulated platelet. Tethers could remain connected with the platelet body or be eventually severed, which occurred preferentially at shear rates above 6,000 s−1. Depending on the length of the severed membrane fragment they represented either isolated tethers or microparticles (arrowheads; see Figure below), the latter defined by a diameter of 50 to 100 nanometers. The shear rate threshold for microparticle formation was between 6,000 s−1 and 10,000 s−1. Immuno-fluorescence and immuno-electron microscopy showed glycoprotein Ibα clustered in DAPs of microparticles and tethers, i.e. the contact sites with the surface immobilized VWF. The microparticles also exhibited tissue factors on their surface and showed significant procoagulant activity measured by thrombin generation. We propose that after GPIbα anchoring to VWF in flowing blood passive mechanical pulling of membrane from platelets may generate platelet derived microparticles that can potentially support thrombogenesis. Figure Figure

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