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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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Published: Swansea 2021
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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first_indexed 2021-05-06T15:32:58Z
last_indexed 2021-05-07T03:23:07Z
id cronfa56815
recordtype RisThesis
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spelling 2021-05-06T17:30:44.4538609 v2 56815 2021-05-06 Development of a novel haemorheological biomarker of clot lysis f9e7beebb05a24f2c566c5014ec5f842 BETHAN MORGAN BETHAN MORGAN true false 2021-05-06 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. E-Thesis Swansea Haemorheology, Fibrinolysis, Coagulation, Gel point 12 4 2021 2021-04-12 10.23889/SUthesis.56815 COLLEGE NANME COLLEGE CODE Swansea University Hawkins, Karl, M. ; Evans, Adrian Doctoral Ph.D EPSRC DTA, Swansea University 2021-05-06T17:30:44.4538609 2021-05-06T16:29:03.3276775 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine BETHAN MORGAN 1 Under embargo Under embargo 2021-05-06T16:58:50.7615391 Output 39976048 application/pdf E-Thesis – open access true 2024-04-12T00:00:00.0000000 Copyright: The author, Bethan Hannah Morgan, 2021. true eng
title Development of a novel haemorheological biomarker of clot lysis
spellingShingle Development of a novel haemorheological biomarker of clot lysis
BETHAN MORGAN
title_short Development of a novel haemorheological biomarker of clot lysis
title_full Development of a novel haemorheological biomarker of clot lysis
title_fullStr Development of a novel haemorheological biomarker of clot lysis
title_full_unstemmed Development of a novel haemorheological biomarker of clot lysis
title_sort Development of a novel haemorheological biomarker of clot lysis
author_id_str_mv f9e7beebb05a24f2c566c5014ec5f842
author_id_fullname_str_mv f9e7beebb05a24f2c566c5014ec5f842_***_BETHAN MORGAN
author BETHAN MORGAN
author2 BETHAN MORGAN
format E-Thesis
publishDate 2021
institution Swansea University
doi_str_mv 10.23889/SUthesis.56815
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 0
active_str 0
description 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.
published_date 2021-04-12T04:12:03Z
_version_ 1763753825172193280
score 11.014067

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