Combined effects of upstream priming and hematocrit on downstream platelet-material interactions

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Title Combined effects of upstream priming and hematocrit on downstream platelet-material interactions
Publication Type thesis
School or College College of Engineering
Department Biomedical Engineering
Author Pumford, Elizabeth Anne
Date 2019
Description Platelet activation plays a crucial role in hemostasis and normal wound healing. However, following vascular device implantation, the same platelet response can lead to device failure. When such a device is implanted, platelet-activating proteins are exposed at the anastomotic sites, and serum proteins adsorb onto the biomaterial surface. This increases platelet adhesion to the surface, leading to activation and increased risk of thrombosis. While it has been shown that upstream priming increases downstream platelet adhesion, there has been limited research examining platelet-surface contacts prior to adhesion. To better understand transient platelet interactions prior to adhesion, this thesis examines the mechanics of platelet rolling on agonists following upstream priming, as well as the effect of platelet-to-red blood cell (RBC) ratio on these interactions. Using a biomimetic microfluidic channel, representative of a vascular graft, platelet-activating agonists were covalently attached in upstream priming, center rolling, and downstream capture positions. Platelet contacts with the rolling agonist were recorded and analyzed, as either plasma reconstituted with variable hematocrit, or varied volume fractions of whole blood, were perfused through the channel. For the proteins tested, platelet pause events on the rolling agonist increased after upstream priming, indicating that transient platelet interactions with upstream agonists pre-activate platelets for increased downstream pause events. Hematocrit had an additional iv effect on platelet priming, as platelet pause events increased as a function of hematocrit up to 20%, declining thereafter. These results suggest that at higher volume fractions of RBCs, there are opposing phenomena as platelet flux to the surface increases platelet-agonist contacts, but RBCs may have increased potential to dislodge arrested platelets. Such postulate seemed to be confirmed through hemodilution perfusion experiments, as the maximum net platelet adhesion occurred at a whole blood volume fraction of 0.5, corresponding to a hematocrit of 20%. These findings suggest that upstream priming increases the frequency of platelet pause events and is further enhanced by the addition of small volumes of RBCs. An improved understanding of primed platelet mechanics, as a function of hematocrit, will contribute to the translation of these results to whole blood applications and the development of improved vascular devices.
Type Text
Publisher University of Utah
Dissertation Name Master of Science
Language eng
Rights Management (c) Elizabeth Anne Pumford
Format application/pdf
Format Medium application/pdf
ARK ark:/87278/s6mh3p7t
Setname ir_etd
ID 1701249
Reference URL https://collections.lib.utah.edu/ark:/87278/s6mh3p7t
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