The role of bone marrow in thrombus resolution

Student thesis: Doctoral ThesisDoctor of Philosophy

Abstract

Deep vein thrombosis (DVT) is a common condition affecting 1-2% of the population. It can be further complicated by serious sequelae such as life threatening pulmonary embolus and the chronically debilitating post-thrombotic syndrome. The main treatment modalities available for DVT are only able to limit disease progression, with resolution occurring physiologically. Natural resolution of DVT occurs through a process of thrombus retraction and recanalisation which is comparable to progenitor mediated neovascularisation. The focus of this project was to examine the circulating progenitor cell response to venous thrombosis and to profile the underlying cytokine response. This data was ultimately used, to manipulate the number of circulating progenitor cells and expression of cytokines to enhance the recanalisation process. The presence of venous thrombus produced a bimodal circulating haematopoietic progenitor cell response whilst in the bone marrow compartment progenitor cells were simultaneously depleted. GCSF, GMCSF, VEGF, PIGF and SDF1 were expressed differentially in thrombus, vein wall and plasma, with the laparotomy wound mirroring the cytokine profile of the resolving thrombus. The expression pattern of PIGF in the resolving thrombus was however, unusually specific and not seen in the healing laparotomy wound.
Date of Award2012
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorAlberto Smith (Supervisor) & Matthew Waltham (Supervisor)

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