Effects of Shear Rate on Propagation of Blood Clotting Determined Using Microfluidics and Numerical Simulations

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• 作者：Matthew K. Runyon ; Christian J. Kastrup ; Bethany L. Johnson-Kerner ; Thuong G. Van Ha ; Rustem F. Ismagilov
• 刊名：Journal of the American Chemical Society
• 出版年：2008
• 出版时间：March 19, 2008
• 年：2008
• 卷：130
• 期：11
• 页码：3458 - 3464
• 全文大小：289K
• 年卷期：v.130,no.11(March 19, 2008)
• ISSN：1520-5126

文摘

This paper describes microfluidic experiments with human blood plasma and numerical simulationsto determine the role of fluid flow in the regulation of propagation of blood clotting. We demonstrate thatpropagation of clotting can be regulated by different mechanisms depending on the volume-to-surfaceratio of a channel. In small channels, propagation of clotting can be prevented by surface-bound inhibitorsof clotting present on vessel walls. In large channels, where surface-bound inhibitors are ineffective,propagation of clotting can be prevented by a shear rate above a threshold value, in agreement withpredictions of a simple reaction-diffusion mechanism. We also demonstrate that propagation of clotting ina channel with a large volume-to-surface ratio and a shear rate below a threshold shear rate can be slowedby decreasing the production of thrombin, an activator of clotting. These in vitro results make two predictions,which should be experimentally tested in vivo. First, propagation of clotting from superficial veins to deepveins may be regulated by shear rate, which might explain the correlation between superficial thrombosisand the development of deep vein thrombosis (DVT). Second, nontoxic thrombin inhibitors with high bindingaffinities could be locally administered to prevent recurrent thrombosis after a clot has been removed. Inaddition, these results demonstrate the utility of simplified mechanisms and microfluidics for generatingand testing predictions about the dynamics of complex biochemical networks.