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Effects of shear rate on propagation of blood clotting determined using microfluidics and numerical simulations

Runyon, Matthew K. and Kastrup, Christian J. and Johnson-Kerner, Bethany L. and Van Ha, Thuong G. and Ismagilov, Rustem F. (2008) Effects of shear rate on propagation of blood clotting determined using microfluidics and numerical simulations. Journal of the American Chemical Society, 130 (11). pp. 3458-3464. ISSN 0002-7863. doi:10.1021/ja076301r.

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This paper describes microfluidic experiments with human blood plasma and numerical simulations to determine the role of fluid flow in the regulation of propagation of blood clotting. We demonstrate that propagation of clotting can be regulated by different mechanisms depending on the volume-to-surface ratio of a channel. In small channels, propagation of clotting can be prevented by surface-bound inhibitors of 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 with predictions of a simple reaction-diffusion mechanism. We also demonstrate that propagation of clotting in a channel with a large volume-to-surface ratio and a shear rate below a threshold shear rate can be slowed by 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 deep veins may be regulated by shear rate, which might explain the correlation between superficial thrombosis and the development of deep vein thrombosis (DVT). Second, nontoxic thrombin inhibitors with high binding affinities could be locally administered to prevent recurrent thrombosis after a clot has been removed. In addition, these results demonstrate the utility of simplified mechanisms and microfluidics for generating and testing predictions about the dynamics of complex biochemical networks.

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Ismagilov, Rustem F.0000-0002-3680-4399
Additional Information:Copyright © 2008 American Chemical Society. Published In Issue: March 19, 2008. Received August 21, 2007. This work was funded by the ONR (Grant N000140610630), the NSF CAREER Award (CHE-0349034), and the Camille Dreyfus Teacher-Scholar Awards Program. M.K.R. was supported in part by Burroughs Wellcome Fund Interfaces I.D. 1001774. R.F.I. is a Cottrell Scholar of Research Corporation and an A. P. Sloan Research Fellow. Some of this work was performed at the MRSEC microfluidic facility (funded by the NSF). We thank Jessica M. Price for contributions in writing and editing this manuscript. Supporting Information Available: Detailed procedure for the experiments and numerical simulations. This material is available free of charge via the Internet at
Funding AgencyGrant Number
Camille and Henry Dreyfus FoundationUNSPECIFIED
Burroughs Wellcome Fund Interfaces1001774
Cottrell Scholar of Research CorporationUNSPECIFIED
Alfred P. Sloan FoundationUNSPECIFIED
Issue or Number:11
Record Number:CaltechAUTHORS:20130821-160730150
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:40861
Deposited By: Whitney Barlow
Deposited On:27 Aug 2013 21:11
Last Modified:10 Nov 2021 00:09

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