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Title: Investigations into the role of phosphoinositide 3-kinase (P13K) in platelet priming and antiplatelet resistance
Author: Blair, Thomas Anthony
ISNI:       0000 0004 5917 3424
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2015
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Platelets play a pivotal role in haemostasis and at sites of vascular injury arrest bleeding. Unregulated haemostasis leads to thrombosis and coronary artery disease (CAD). The 'gold-standard' preventative measure to combat CAD is administration of antiplatelet compounds that target TxA2/ ADP amplification pathways. Some CAD patients are 'resistant' to anti platelet therapy and these patients often have hyperactive platelets. In combination with physiological stimuli, primers potentiate platelet functional responses. Primers are known to function via a Pl3K-dependent mechanism and may induce antiplatelet resistance. The aims of this PhD project were: (i) establish the role of primers in anti platelet resistance and (ii) characterise the PI3K isoform involved in primer-mediated platelet potentiation. First, I studied the role of primers in anti platelet resistance by treating platelets with ARC66096 (P2Y12 inhibitor) and/or aspirin in the presence/absence of primers (IGF-l, TPO and adrenaline). This study demonstrated that primers could drive antiplatelet resistance. Furthermore Pl3K-mediated mechanisms were responsible for IGF-l/TPO-mediated resistance, while Pl3K-dependent and independent mechanisms were responsible for adrenaline-mediated resistance.
Supervisor: Hers, Ingeborg Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available