A novel functional assay of antiplatelet drug efficacy was designed by utilizing the phenomena of platelet margination in flowing blood and transient platelet contacts with surface-immobilized platelet agonists. Flow margination enhances transient contacts of platelets with the walls of flow chambers covered with surface-immobilized proteins. Depending on the type and the surface density of the immobilized agonists, such transient interactions could “prime” the marginated platelet subpopulation for enhanced activation and adhesion downstream. By creating an upstream surface patch with an immobilized platelet agonist, platelet flow margination was used to test how effective antiplatelet drugs are in suppressing downstream platelet activation and adhesion. The platelet adhesion downstream was measured by a so-called “capture” patch region close to the distal end of the flow chamber. Platelet adhesion downstream was found to be dose-dependent on the upstream surface coverage of the “priming” patch, with immobilized fibrinogen acting as a platelet agonist. Several antiplatelet agents (acetylsalicylic acid, eptifibatide, and tirofiban) were evaluated for their efficacy in attenuating downstream adhesion after upstream platelet priming. The activation of the platelet population was found to be dependent on both the extent of the upstream agonist stimulus and the antiplatelet drug concentration. Such a relationship provides an opportunity to measure the efficacy of specific antiplatelet agents against the type and concentration of upstream platelet agonists.
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June 2016
Research Article|
March 30 2016
Functional assay of antiplatelet drugs based on margination of platelets in flowing blood
Colin D. Eichinger;
Colin D. Eichinger
Department of Bioengineering,
University of Utah
, Salt Lake City, Utah 84112
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Aaron L. Fogelson;
Aaron L. Fogelson
Department of Mathematics,
University of Utah
, Salt Lake City, Utah 84112
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Vladimir Hlady
Vladimir Hlady
a)
Department of Bioengineering,
University of Utah
, Salt Lake City, Utah 84112
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a)
Author to whom correspondence should be addressed; present address: 20 S 2030 E., Rm. 108A, Salt Lake City, Utah 84112; electronic mail: [email protected]
Biointerphases 11, 029805 (2016)
Article history
Received:
February 10 2016
Accepted:
March 22 2016
Citation
Colin D. Eichinger, Aaron L. Fogelson, Vladimir Hlady; Functional assay of antiplatelet drugs based on margination of platelets in flowing blood. Biointerphases 1 June 2016; 11 (2): 029805. https://doi.org/10.1116/1.4945305
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