Quantitative Characterization of Intra- and Inter-Individual Platelet Heterogeneity for Clinical Biomarker Development
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Bradley, Margaret Grace
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Abstract
Personalized medicine approaches aim to correct the pitfalls of a one-size-fits-all healthcare model, where pre-defined thresholds are used to classify patients as either healthy or diseased. Using diagnostic biomarkers, personalized medicine can characterize a patient’s current health state so that proper diagnosis and treatment plans can be tailored accordingly. However, the biometrics needed to implement these approaches are not yet adequately defined for widespread clinical use and require more research. Defining the role of platelets – a blood cell most associated with wound clotting and vascular repair – in disease manifestation and treatment response may help explain why patients with the same diagnosis demonstrate different health outcomes.
Our study aims to advance the use of platelets as biomarkers to reduce the burden left by a one-size-fits-all healthcare model. Specifically, we aim to quantitatively assess the extent and sources of intra-individual and inter-individual variation in platelet tests in response to agonist and anti-platelet drugs, and how that variation is affected by pre-analytical variables through the quantification of cellular and functional platelet responses via flow cytometry and combined functional clinical assays respectively. Our results reveal that pre-analytical variables such as plate type, PRP/final volume, shaking, and temperature can significantly impact platelet functional responses. When these pre-analytical variables are accounted for, prominent intra-donor variability can be observed across experiments, but inter-individual variability is minimal. These pre-analytical factors must be carefully controlled in future efforts to establish platelet-based personalized biomarkers for clinical use. Additionally, establishing the threshold for which a healthy donor’s platelets can vary in response to both stimulation and anti-platelet drugs is essential to enable use of platelet-based therapeutics in the clinic.
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Undergraduate Research Option Thesis