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High Shear Dependent von Willebrand Factor Self-assembly Fostered by Platelet Interaction and Controlled by ADAMTS13

High Shear Dependent von Willebrand Factor Self-assembly Fostered by Platelet Interaction and Controlled by ADAMTS13

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KRAGH, Thorsten, Marina NAPOLEONE, Mohammad A. FALLAH, Herbert GRITSCH, Matthias F. SCHNEIDER, Armin J. REININGER, 2014. High Shear Dependent von Willebrand Factor Self-assembly Fostered by Platelet Interaction and Controlled by ADAMTS13. In: Thrombosis Research. 133(6), pp. 1079-1087. ISSN 0049-3848. eISSN 1879-2472

@article{Kragh2014Shear-30033, title={High Shear Dependent von Willebrand Factor Self-assembly Fostered by Platelet Interaction and Controlled by ADAMTS13}, year={2014}, doi={10.1016/j.thromres.2014.03.024}, number={6}, volume={133}, issn={0049-3848}, journal={Thrombosis Research}, pages={1079--1087}, author={Kragh, Thorsten and Napoleone, Marina and Fallah, Mohammad A. and Gritsch, Herbert and Schneider, Matthias F. and Reininger, Armin J.} }

Gritsch, Herbert 2015-02-25T09:29:07Z Napoleone, Marina Fallah, Mohammad A. Schneider, Matthias F. eng Gritsch, Herbert Fallah, Mohammad A. Napoleone, Marina Reininger, Armin J. Kragh, Thorsten Schneider, Matthias F. 2015-02-25T09:29:07Z Kragh, Thorsten High Shear Dependent von Willebrand Factor Self-assembly Fostered by Platelet Interaction and Controlled by ADAMTS13 Reininger, Armin J. 2014 Introduction<br /><br />The paradigm of activation induced platelet aggregation has recently been refuted under blood flow conditions with shear rates exceeding 20,000 s<sup>- 1</sup>. These lead to reversible rolling platelet aggregates, which were dependent on the presence of immobilized and soluble von Willebrand factor.<br /><br />Material and Methods<br /><br />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 50,000 s<sup>- 1</sup>. Washed blood cell suspension containing recombinant von Willebrand factor (rVWF) was perfused over rVWF or collagen coated surfaces.<br /><br />Results<br /><br />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 20,000 s<sup>- 1</sup> 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 7-8 minutes. Changing wall parallel flow to stagnation point flow halved the required shear rate threshold.<br /><br />Conclusion<br /><br />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.

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