Fosbury, Emma Louise;
(2020)
Studies of acquired and inherited coagulopathy using the thrombin generation assay.
Doctoral thesis (M.D(Res)), UCL (University College London).
Preview |
Text
Fosbury_000_Thesis.pdf Download (8MB) | Preview |
Abstract
In order to survive, an individual’s haemostatic system has to have the capacity to respond promptly to injury and thrombus formation has to occur in a highly regulated fashion. Over the past two hundred years, our understanding of this complex system has increased dramatically. It is perhaps surprising, therefore, that clinicians rely predominantly on assays to assess coagulation that were developed over 50 years ago and that only assess the time to initial clot formation. This reflects the challenge of truly understanding the complex dynamic contributions of platelets, vascular endothelium and coagulation factors under shear force and replicating this in a test-tube. There has therefore been a drive to develop better methods of detecting disordered haemostasis that can be accurately correlated with bleeding or thrombotic risk and that can be utilised to guide treatment. The thrombin generation assay is currently a research tool that is able to chart the different phases of thrombin generation, recognising that the majority of this occurs after the end-point of traditional coagulation assays. Thrombin is key to effective haemostasis and the thrombin generation assay has been shown to correlate with a range of bleeding and thrombotic states. Although it is recognised to produce valuable information, it is hampered by the impact of pre-analytical variables, lack of standardisation and inter-operator and inter-laboratory variability. Optimisation of the assay as well as development of normal reference ranges is key. This is in addition to further phenotyping of dysfunctional haemostasis and providing evidence of clinical relevance. This thesis sets out to address these different areas with studies including the generation of normal reference ranges in addition to examining the sensitivity of the assay to anticoagulation (and its reversal) as well as exploring potential factors contributing to the variable bleeding phenotype seen in patients with severe haemophilia.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | M.D(Res) |
| Title: | Studies of acquired and inherited coagulopathy using the thrombin generation assay |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2020. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10091271 |
Archive Staff Only
 |
View Item |
