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Electron confocal and atomic force microscopic analysis of platelets fibrin and erythrocytes in atopic asthma
Thesis (PhD)--University of Pretoria, 2018.
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University of Pretoria
2018
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| _version_ | 1867613626679951360 |
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| access_status_str | Open Access |
| author2 | Pretorius, Etheresia |
| author_browse | Pretorius, Etheresia |
| author_facet | Pretorius, Etheresia |
| collection | Thesis |
| dc_rights_str_mv | � 2018 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. |
| description | Thesis (PhD)--University of Pretoria, 2018. |
| format | Thesis |
| id | oai:repository.up.ac.za:2263/67999 |
| institution | University of Pretoria (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:39:08.341Z |
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| provenance_str_mv | Harvested via OAI-PMH from UPSpace — University of Pretoria Institutional Repository |
| publishDate | 2018 |
| publishDateRange | 2018 |
| publishDateSort | 2018 |
| publisher | University of Pretoria |
| publisherStr | University of Pretoria |
| record_format | dspace |
| source_str | UPSpace — University of Pretoria Institutional Repository |
| spelling | oai:repository.up.ac.za:2263/67999 Electron confocal and atomic force microscopic analysis of platelets fibrin and erythrocytes in atopic asthma Pretorius, Etheresia sajee.alummoottil@up.ac.za Phulukdaree, Alisa Van Rooy, Mia-Jeanne Alummoottil, Sajee UCTD Unrestricted SDG-03: Good health and well-being Thesis (PhD)--University of Pretoria, 2018. Background: The underlying risk factor of non-communicable diseases is inflammation. The pathophysiology of asthma and/or allergic asthma is also, no surprisingly, also linked to chronic inflammation. The prevalence and incidence of asthma is on the increase, despite of a variety of treatment modalities. Asthma therefore is a growing burden on healthcare system and on society. Asthma pathophysiology is not only linked to inflammation, but also with activation of coagulation and reduced fibrinolysis due to plasma and locally derived factors in the airways. Alterations to these factors may thus influence the biophysical and mechanical properties of the coagulation, fibrin deposition followed by asthma pathology. Methodology: The objective of this study was to evaluate changes of blood components in asthma patients (n=30) compared to controls (n=30) using routine haematology screening using a haematology analyser; structural changes and axial ratio analysis using light microscopy (erythrocytes), elasticity using atomic force microscopy (erythrocytes); ultrastructural changes using scanning electron microscopy (erythrocytes, platelets and fibrin), transmission electron microscopy (platelets) and confocal microscopy (platelets) as well as the viscoelastic properties of the fibrin clot using thromboelastography; and mRNA levels of FXIII-A in whole blood by quantitative PCR. Results: The haematology findings of controls and asthma patients were within normal clinical ranges. There was, however, a significantly higher level of circulating monocytes (p=0.0066), erythrocytes (p=0.0004), haemoglobin (p=0.0057) and haematocrit (p=0.0049). The analysis of eosin stained erythrocytes by light microscopy showed more echinocytes, acanthocytes and ovalocytes compared to controls and the axial ratio was also significantly higher (controls: 1.2�0.22nm vs. asthma: 1.165�0.16nm, p<0.0001). Atomic force microscopy findings showed significantly reduced erythrocyte membrane elasticity (p=0.001). Morphological changes of erythrocytes were also noted from scanning electron microscopy. Platelet morphology and ultrastructure were qualitatively assessed using scanning electron microscopy, transmission electron microscopy and confocal microscopy and showed morphological changes indicative of platelet activation in asthma samples. In addition, the assessment of clot kinetics by thromboelastography also showed alteration with a tendency to produce stronger fibrin clots in asthma samples. The reaction time was higher (p<0.0001), alpha-angle was lower (p<0.0001), maximum rate of clot formation was higher (p<0.0001) � all indicative of a longer time for clotting to occur but the maximal amplitude which is indicative of clot strength and stability was significantly higher in asthma samples (p=0.0478). As the aggregation and cross-linking of fibrin fibres depends on factor XIII (FXIII), its excessive production may lead to alterations in fibrin polymerisation and crosslinking resulting in stronger fibrin clot formation and resistance to fibrinolysis. Densitometry analysis of scanning electron microscopy images of fibrin fibres showed a significantly lower variance in asthma samples (p<0.0001) indicative of more matt like structures compared to normal fibrin fibres in controls. The analysis of gene expression by qPCR revealed a significant 17.34-fold higher FXIII-A mRNA level in whole blood of asthma patients compared to controls indicating greater potential for de novo production of FXIII-A compared to the control group. These results would facilitate further research possibilities for identifying potential biomarkers in allergic asthma. These findings support the hypothesis of this study: enhanced coagulation may be attributed to the altered morphology and activation of platelets, erythrocyte and fibrin networks in asthma. Conclusion: In conclusion, altered erythrocyte and platelet morphology, excess production of FXIII-A, altered fibrin architecture and clot properties affects the coagulation profile in asthma, systemically. Further research is needed to extrapolate exact mechanism by which increased systemic coagulation contributes to the pathophysiology of the disease locally. em2026 Physiology PhD SDG-03: Good health and well-being 2018-12-05T08:06:25Z 2018-12-05T08:06:25Z 2009/08/18 2018 Thesis Alummoottil, S 2018, Electron confocal and atomic force microscopic analysis of platelets fibrin and erythrocytes in atopic asthma, PhD Thesis, University of Pretoria, Pretoria, viewed yymmdd <http://hdl.handle.net/2263/67999> S2018 http://hdl.handle.net/2263/67999 en � 2018 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. application/pdf University of Pretoria |
| spellingShingle | UCTD Unrestricted SDG-03: Good health and well-being Electron confocal and atomic force microscopic analysis of platelets fibrin and erythrocytes in atopic asthma |
| title | Electron confocal and atomic force microscopic analysis of platelets fibrin and erythrocytes in atopic asthma |
| title_full | Electron confocal and atomic force microscopic analysis of platelets fibrin and erythrocytes in atopic asthma |
| title_fullStr | Electron confocal and atomic force microscopic analysis of platelets fibrin and erythrocytes in atopic asthma |
| title_full_unstemmed | Electron confocal and atomic force microscopic analysis of platelets fibrin and erythrocytes in atopic asthma |
| title_short | Electron confocal and atomic force microscopic analysis of platelets fibrin and erythrocytes in atopic asthma |
| title_sort | electron confocal and atomic force microscopic analysis of platelets fibrin and erythrocytes in atopic asthma |
| topic | UCTD Unrestricted SDG-03: Good health and well-being |
| url | http://hdl.handle.net/2263/67999 |