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Title: Platelet and vascular studies in myeloproliferative disorders
Author: Lynch, Susan Fraser
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2008
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We have studied a cohort of patients with polycythaemia vera (PV) primary thrombocythaemia (PT) and primary myelofibrosis (PMF) and described their clinical and laboratory features in comparison to other published observations. The demographic, haematological and molecular characteristics of our cohort were similar to other retrospective analyses, but the occurrence of thrombo-haemorrhagic complications was lower. The presence of vascular abnormalities in these patients was investigated using both established markers and an assay was devised to measure platelet, endothelial, leucocytes and red cell microparticles in platelet poor plasma using flow cytometry techniques. This assay was optimised for pre-analytical variables, the most important of which was found to be sample centrifugation. In keeping with previous studies, increased platelet activation was observed in PV and PT patients compared to healthy controls using both established markers and as evidenced by increased numbers of platelet microparticles. There was no evidence of endothelial disturbance using the soluble endothelial marker E-selectin but we did observe elevated endothelial microparticles in patients compared to controls. Microparticles may therefore be useful as a marker of vascular abnormalities in these disorders and in view of their prothrombotic properties may be an additional pathogenic mechanism in the prothrombotic state and a potential therapeutic target. In relation to bone marrow fibrosis, plasma levels of platelet α-granule contents, including the pro-fibrotic cytokine transforming growth factor β (TGFβ), were studied. We observed elevated levels of TGFβ in patients compared to controls, with the highest levels in patients with PMF and in those with PT or PV who had more marked fibrosis. Further, levels of TGFβ were strongly associated with another α-granule protein beta-thromboglobulin, suggesting that platelet α-granules may be an important source for this pro-fibrotic cytokine.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available