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Aspirin in diabetes mellitus: mechanisms and clinical implications

Kurdee, Zeyad Shafiq (2015) Aspirin in diabetes mellitus: mechanisms and clinical implications. PhD thesis, University of Leeds.

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Diabetes is characterised by increased activation of platelets and coagulation factors, contributing to the high risk of cardiovascular disease in these individuals. Aspirin is a classic antiplatelet agent used for the protection from atherothrombotic disease. Clinical evidence suggests the efficacy of this agent is reduced in diabetes, by mechanisms that are not entirely clear. I hypothesise that the reduced clinical efficacy of aspirin in diabetes is related to a compromise in the effects of this agent on both the cellular and fluid phase of coagulation, secondary to elevated blood glucose levels. Using a combination of ex vivo/in vivo aspirin experiments in patients with type 1 diabetes and healthy controls, I demonstrate reduced platelet inhibition by low aspirin concentration in diabetes, which appears to be related to both medium term as well as instantaneous hyperglycaemia. This suggests that current treatment strategies of administering aspirin once daily in diabetes are inadequate. Moreover, I show that the fibrinolytic properties of aspirin are reduced in diabetes, which may be related to reduce acetylation of one or more plasma protein other than fibrinogen. Finally, I describe a potential mechanism for aspirin, related to the effect of this agent on platelet-fibrinogen interaction, an effect that is also compromised in patients with diabetes. In conclusion, my data indicate that both medium term and immediate hyperglycaemia modulate the effects of aspirin on the cellular and protein arm of coagulation. Future work is required to understand the best glycaemic indices that optimise response to aspirin in diabetes. Moreover, additional studies are necessary to clarify the role of alternative dosing strategies for aspirin in patients with diabetes

Item Type: Thesis (PhD)
Keywords: Aspirin, Diabetes, Platelet, Fibrinogen
Academic Units: The University of Leeds > Faculty of Medicine and Health (Leeds) > Leeds Institute of Genetics, Health and Therapeutics (LIGHT) > Academic Unit of Cardiovascular Medicine (Leeds)
The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds)
Identification Number/EthosID: uk.bl.ethos.669625
Depositing User: Mr Zeyad Kurdee
Date Deposited: 16 Nov 2015 12:53
Last Modified: 25 Nov 2015 13:49
URI: http://etheses.whiterose.ac.uk/id/eprint/10750

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