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Large Amplitude Oscillatory Shear (LAOS) studies of fibrin and whole blood clots / Tunde F. Lamer

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DOI (Published version): 10.23889/Suthesis.46063

Abstract

Venous Thromboembolism encompasses a progression of diseases where initially a blood clot is formed in the deep veins. The clot can break off, travel in the bloodstream and lodge in the pulmonary arteries leading to a lack of blood supply to the lungs. This embolic event known as pulmonary embolism...

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Published: 2018
Institution: Swansea University
Degree level: Doctoral
Degree name: Ph.D
URI: https://cronfa.swan.ac.uk/Record/cronfa46063
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first_indexed 2018-11-23T20:19:41Z
last_indexed 2019-10-21T16:52:19Z
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spelling 2018-11-26T09:24:46.7548461 v2 46063 2018-11-23 Large Amplitude Oscillatory Shear (LAOS) studies of fibrin and whole blood clots 2018-11-23 Venous Thromboembolism encompasses a progression of diseases where initially a blood clot is formed in the deep veins. The clot can break off, travel in the bloodstream and lodge in the pulmonary arteries leading to a lack of blood supply to the lungs. This embolic event known as pulmonary embolism can often be fatal but is difficult to predict. This thesis investigates the nonlinear rheological properties of blood clots that are important for understanding the mechanisms of embolism. The work presented uses the advanced rheological technique, Large Amplitude Oscillatory Shear (LAOS) in both strain-controlled (LAOStrain) and stress-controlled (LAOStress) modes in order to characterise the nonlinear viscoelastic properties of fibrin and whole blood clots. Furthermore, the role of clot microstructure in the nonlinear viscoelastic properties of the mature clot was investigated. Alternating application of LAOS and Small Amplitude Oscillatory Shear (SAOS) provided detailed information of reversible and irreversible structural changes of the fibrin network revealing several distinct regions of nonlinear viscoelastic behaviour up to the point of network fracture. Shifting of these regions to different levels of stress was seen in fibrin and whole blood clots formed with different microstructures as manipulated by the addition of thrombin or heparin. Of significance, the rheologically derived value of fractal dimension, obtained from the measurement of a Gel Point using SAOS, correlated with the eventual fracture stress in a LAOStress measurement. This work suggests that incipient clot microstructure influences the ability of the fully formed clot to resist fracture as a consequence of haemodynamic forces encountered in blood vessels and sheds light on the mechanisms of changes in the conformation of the fibrin network up to the point of fracture. A main conclusion of this thesis is that the measurement of a fractal dimension of a blood clot may serve as a much needed biomarker for predicting embolism in patients whom experience thrombosis. E-Thesis 31 12 2018 2018-12-31 10.23889/Suthesis.46063 A selection of third party content is redacted or is partially redacted from this thesis. COLLEGE NANME COLLEGE CODE Swansea University Doctoral Ph.D 2018-11-26T09:24:46.7548461 2018-11-23T16:30:19.3323645 Swansea University Medical School Medicine Tunde F. Lamer 1 0046063-23112018164721.pdf Lamer_Tunde_F_Final_PhD_Thesis_Redacted.pdf 2018-11-23T16:47:21.1700000 Output 29620189 application/pdf Redacted version - open access true 2018-11-23T00:00:00.0000000 A selection of third party content is redacted or is partially redacted from this thesis. true
title Large Amplitude Oscillatory Shear (LAOS) studies of fibrin and whole blood clots
spellingShingle Large Amplitude Oscillatory Shear (LAOS) studies of fibrin and whole blood clots
,
title_short Large Amplitude Oscillatory Shear (LAOS) studies of fibrin and whole blood clots
title_full Large Amplitude Oscillatory Shear (LAOS) studies of fibrin and whole blood clots
title_fullStr Large Amplitude Oscillatory Shear (LAOS) studies of fibrin and whole blood clots
title_full_unstemmed Large Amplitude Oscillatory Shear (LAOS) studies of fibrin and whole blood clots
title_sort Large Amplitude Oscillatory Shear (LAOS) studies of fibrin and whole blood clots
author ,
author2 Tunde F. Lamer
format E-Thesis
publishDate 2018
institution Swansea University
doi_str_mv 10.23889/Suthesis.46063
college_str Swansea University Medical School
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hierarchy_top_id swanseauniversitymedicalschool
hierarchy_top_title Swansea University Medical School
hierarchy_parent_id swanseauniversitymedicalschool
hierarchy_parent_title Swansea University Medical School
department_str Medicine{{{_:::_}}}Swansea University Medical School{{{_:::_}}}Medicine
document_store_str 1
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description Venous Thromboembolism encompasses a progression of diseases where initially a blood clot is formed in the deep veins. The clot can break off, travel in the bloodstream and lodge in the pulmonary arteries leading to a lack of blood supply to the lungs. This embolic event known as pulmonary embolism can often be fatal but is difficult to predict. This thesis investigates the nonlinear rheological properties of blood clots that are important for understanding the mechanisms of embolism. The work presented uses the advanced rheological technique, Large Amplitude Oscillatory Shear (LAOS) in both strain-controlled (LAOStrain) and stress-controlled (LAOStress) modes in order to characterise the nonlinear viscoelastic properties of fibrin and whole blood clots. Furthermore, the role of clot microstructure in the nonlinear viscoelastic properties of the mature clot was investigated. Alternating application of LAOS and Small Amplitude Oscillatory Shear (SAOS) provided detailed information of reversible and irreversible structural changes of the fibrin network revealing several distinct regions of nonlinear viscoelastic behaviour up to the point of network fracture. Shifting of these regions to different levels of stress was seen in fibrin and whole blood clots formed with different microstructures as manipulated by the addition of thrombin or heparin. Of significance, the rheologically derived value of fractal dimension, obtained from the measurement of a Gel Point using SAOS, correlated with the eventual fracture stress in a LAOStress measurement. This work suggests that incipient clot microstructure influences the ability of the fully formed clot to resist fracture as a consequence of haemodynamic forces encountered in blood vessels and sheds light on the mechanisms of changes in the conformation of the fibrin network up to the point of fracture. A main conclusion of this thesis is that the measurement of a fractal dimension of a blood clot may serve as a much needed biomarker for predicting embolism in patients whom experience thrombosis.
published_date 2018-12-31T04:02:12Z
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score 10.8434725