A Microfluidic Model of Hemostasis Sensitive to Platelet Function and Coagulation
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Hemostasis is the process of sealing a vascular injury with a thrombus to arrest bleeding. The type of thrombus that forms depends on the nature of the injury and hemodynamics. There are many models of intravascular thrombus formation whereby blood is exposed to prothrombotic molecules on a solid substrate. However, there are few models of extravascular thrombus formation whereby blood escapes into the extravascular space through a hole in the vessel wall. Here, we describe a microfluidic model of hemostasis that includes vascular, vessel wall, and extravascular compartments. Type I collagen and tissue factor, which support platelet adhesion and initiate coagulation, respectively, were adsorbed to the wall of the injury channel and act synergistically to yield a stable thrombus that stops blood loss into the extravascular compartment in ~ 7.5 min. Inhibiting factor VIII to mimic hemophilia A results in an unstable thrombus that was unable to close the injury. Treatment with a P2Y12 antagonist to reduce platelet activation prolonged the closure time two-fold compared to controls. Taken together, these data demonstrate a hemostatic model that is sensitive to both coagulation and platelet function and can be used to study coagulopathies and platelet dysfunction that result in excessive blood loss.
keywordsBiorheology Biotransport Platelets Coagulation
This work was supported by a NSF CAREER (CBET-1351672), American Heart Association (14GRNT20410094), and the National Institutes of Health (R01HL120728, R21NS082933).
No animal studies were carried out by the authors for this article.
Conflict of Interest
The authors R. M. Schoeman, K. Rana, N. Danes, and M. Lehmann declare that they have no conflicts of interest. J. A. Di Paola, A. L. Fogelson, K. Leiderman, and K. B. Neeves reports Grants from NIH and NSF. A. L. Fogelson reports personal fees from Genentech outside the submitted work.
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (University of Colorado, Boulder) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all subjects for being included in the study.
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