title: Effects of shear rate on propagation of blood clotting determined using microfluidics and numerical simulations.
abstract: 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.
authors.affiliation: Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Runyon
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Kastrup
authors.forename: Bethany L
authors.initials: BL
authors.lastname: Johnson-Kerner
authors.forename: Thuong G Van
authors.initials: TG
authors.lastname: Ha
authors.forename: Rustem F
authors.initials: RF
authors.lastname: Ismagilov
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects; D001783:Blood Flow Velocity / Q000502:physiology; D003198:Computer Simulation; D006801:Humans; D044085:Microfluidics / Q000379:methods*; D009716:Numerical Analysis, Computer-Assisted; D033081:Shear Strength; D013917:Thrombin / Q000037:antagonists & inhibitors; D013927:Thrombosis / Q000517:prevention & control; D014914:Whole Blood Coagulation Time
chemical_list: D000925:Anticoagulants; D013917:Thrombin