Contractile forces in platelet aggregates under microfluidic shear gradients reflect platelet inhibition and bleeding risk

Lucas H. Ting, Shirin Feghhi, Nikita Taparia, Annie O. Smith, Ari Karchin, Esther Lim, Alex St. John, Xu Wang, Tessa Rue, Nathan J. White () and Nathan J. Sniadecki ()
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Lucas H. Ting: University of Washington
Shirin Feghhi: University of Washington
Nikita Taparia: University of Washington
Annie O. Smith: University of Washington
Ari Karchin: University of Washington
Esther Lim: University of Washington
Alex St. John: University of Washington
Xu Wang: University of Washington
Tessa Rue: University of Washington
Nathan J. White: University of Washington
Nathan J. Sniadecki: University of Washington

Nature Communications, 2019, vol. 10, issue 1, 1-10

Abstract: Abstract Platelets contract forcefully after their activation, contributing to the strength and stability of platelet aggregates and fibrin clots during blood coagulation. Viscoelastic approaches can be used to assess platelet-induced clot strengthening, but they require thrombin and fibrin generation and are unable to measure platelet forces directly. Here, we report a rapid, microfluidic approach for measuring the contractile force of platelet aggregates for the detection of platelet dysfunction. We find that platelet forces are significantly reduced when blood samples are treated with inhibitors of myosin, GPIb-IX-V, integrin αIIbβ3, P2Y12, or thromboxane generation. Clinically, we find that platelet forces are measurably lower in cardiology patients taking aspirin. We also find that measuring platelet forces can identify Emergency Department trauma patients who subsequently require blood transfusions. Together, these findings indicate that microfluidic quantification of platelet forces may be a rapid and useful approach for monitoring both antiplatelet therapy and traumatic bleeding risk.

Date: 2019
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DOI: 10.1038/s41467-019-09150-9

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