Threshold Response of Initiation of Blood Coagulation by Tissue Factor in Patterned Microfluidic Capillaries Is Controlled by Shear Rate
Abstract
Objective—Blood flow is considered one of the important parameters that contribute to venous thrombosis. We quantitatively test the relationship between initiation of coagulation and shear rate and suggest a biophysical mechanism to understand this relationship. Methods and Results—Flowing human blood and plasma were exposed to cylindrical surfaces patterned with patches of tissue factor (TF) by using microfluidics. Initiation of coagulation of normal pooled plasma depended on shear rate, not volumetric flow rate or flow velocity, and coagulation initiated only at shear rates below a critical value. Initiation of coagulation of platelet-rich plasma and whole blood showed similar behavior. At constant shear rate, coagulation of plasma also showed a threshold response to the size of a patch of TF, consistent with our previous work in the absence of flow. Conclusion—Initiation of coagulation of flowing blood displays a threshold response to shear rate and to the size of a surface patch of TF. Combined with the results of others, these results set the range of shear rates that limit initiation of coagulation by small surface areas of TF and by shear activation of platelets. This range fits the relatively narrow range of physiological shear rates described by Murray's law. (Arterioscler Thromb Vasc Biol. 2008;28:2035-2041)
Additional Information
Copyright © 2008 by American Heart Association. Original received May 13, 2008; final version accepted August 5, 2008. Published online before print August 14, 2008. We thank Matthew Runyon, Howard Stone, and Thuong Van Ha for helpful discussions, Pamela Haltek and Sharice Davis for collecting blood samples, and Jessica M. Price for contributions in writing and editing this manuscript. Sources of Funding: This work was supported in part by NSF CAREER Award No. CHE-0349034 and ONR grant No. N000140610630. 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 Materials Research Science and Engineering Center microfluidic facility funded by the NSF.Additional details
- Eprint ID
- 40866
- Resolver ID
- CaltechAUTHORS:20130821-160731095
- CHE-0349034
- NSF
- N000140610630
- ONR
- Cottrell Scholar of Research Corporation
- Alfred P. Sloan Foundation
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2013-08-27Created from EPrint's datestamp field
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2021-11-10Created from EPrint's last_modified field