E-Thesis 151 views
Development of a novel haemorheological biomarker of clot lysis / BETHAN MORGAN
Swansea University Author: BETHAN MORGAN
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DOI (Published version): 10.23889/SUthesis.56815
Abstract
Thrombosis is a leading contributor to death and disability, carrying high social and healthcare costs. Current treatment protocols in patients presenting with blood clots (such as those with ischemic stroke) recommend the administration of thrombolytic drugs; however, this option is associated with...
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Swansea
2021
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| Institution: | Swansea University |
| Degree level: | Doctoral |
| Degree name: | Ph.D |
| Supervisor: | Hawkins, Karl, M. ; Evans, Adrian |
| URI: | https://cronfa.swan.ac.uk/Record/cronfa56815 |
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| Abstract: |
Thrombosis is a leading contributor to death and disability, carrying high social and healthcare costs. Current treatment protocols in patients presenting with blood clots (such as those with ischemic stroke) recommend the administration of thrombolytic drugs; however, this option is associated with severe haemorrhagic side effects. Clinicians currently have access to a wide range of fibrinolytic biomarkers; however, these either rely on monitoring a single component of the fibrinolytic system or use arbitrary definitions of lysis, and thus have limited value.This thesis presents the development and validation of a novel haemorhe-ological biomarker, utilising advanced rheological techniques that measure fibrinol-ysis through the detection of a gel and de-gel point. This provides a global marker of coagulation and lysis based on the period of haemostatic functionality, i.e. the clots lifetime as a viscoelastic solid. This biomarker was evaluated in samples of blood and plasma, and the results demonstrate its potential use as a tool for the monitoring and development of thrombolytic therapies.The work herein also investigates the influence of shear induced modifi-cation of clot structure on clot lysis through the use of controlled stress parallel superposition rheometry. Clots formed under increasing levels of shear stress were found to have increased resistance to lysis, a finding which has significance in-vivo when considering pathophysiologically relevant changes to flow, due to high blood pressure and narrowing of blood vessels. Finally, the effects of platelet mediated contraction were shown to have a negligible impact on the rheological measurements and the associated biomarker. This represents a significant advan-tage over current mechanical based techniques, such as thromboelastometry and thromboelastography. |
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| Keywords: |
Haemorheology, Fibrinolysis, Coagulation, Gel point |
| College: |
Faculty of Medicine, Health and Life Sciences |