Haemostatic and thrombotic disorders: a journey from bench to bedside
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Date
2019-12
Authors
Meiring, Sarah Muriel
Journal Title
Journal ISSN
Volume Title
Publisher
University of the Free State
Abstract
This compilation focuses on thrombotic and haemostatic disorders, illustrating my journey from basic research on thrombotic and haemostatic disorders to the differential diagnoses of these disorders. For purposes of clarity I shall divide it in three parts. The first part includes the testing of antithrombotic agents. My scientific career started with the testing of antithrombotic drugs in a baboon model of arterial thrombosis. These antithrombotic drugs were mostly targeted at platelets and, to a lesser extent, coagulation. For my PhD, I clarified the catabolism, pharmacokinetics and exctretion of recombinant hirudin, an anti-thrombin drug. The second part includes the development of cost-effective diagnostic tests, mostly for von Willebrand disease (VWD), the most common congenital bleeding disorder. This comprises the largest part of the thesis. I developed four anti-thrombotic peptides by using Phage Display technology that I mastered during my post-doctoral study at the University of Leuven in Belgium. I was also part of the group of researchers that developed many new thrombosis models in baboons. For my M.Med Sc study, I developed a flow chamber model to study in vitro endothelial function, which was subsequently used to test the thrombogenicity of tissue-engineered small vessels. This study was the first where endothelial cells were successfully seeded onto decellularised baboon arteries. This study was undertaken in collaboration with the Department of Cardiothoracic Surgery at the University of the Free State, Bloemfontein. The third part is a spin-off from my research on VWD. I established the only Special Haemostasis laboratory of the NHLS, situated at the University of the Free State in Bloemfontein, South Africa, by developing, validating and implementing four diagnostic assays. As a result the laboratory now functions as a reference centre for von Willebrand disease; the most prevalent, but underdiagnosed bleeding disorder in South Africa. The developed diagnostic assays resulted in nineteen peer-reviewed publications on the diagnosis of haemostatic and thrombotic disorders. As reference centre for VWD in South Africa, we published eight articles on its diagnosis, together with international leaders in the field. Additionally, we also published the first South African recommendations regarding the differential diagnoses of VWD. We published on other bleeding disorders and on a fatal thrombotic disorder, thrombotic thrombocytopenic purpura (TTP). Lastly, is it important to note that the research on VWD, haemophilia and TTP is ongoing.
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Keywords
Thesis (Ph.D. (Haematology))--University of the Free State, 2019, Thrombotic disorders, Thrombosis, Haemophilia, Antithrombotic agents, Diagnosis, Diagnostic agents, Von Willebrand disease