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Title: Haematological and clinical factors influencing thrombus formation, structure and fibrinolysis
Author: Jones, Chris I.
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2007
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This work investigates how changes in the thrombus over time, and in the action of platelets, brought about by physiological or therapeutic factors, influence the susceptibility of thrombi to fibrinolysis. Resistance to fibrinolysis increased with thrombus age, and was associated with expression and/or release of FXIII, TAFI, PAI-1, and FXI, by cells within the thrombus, the recruitment of which was largely platelet dependant. Platelets increase resistance to fibrinolysis through release of FXIII and TAFI, and act pro-fibrinolytically through the recruitment of monocytes, and, by a yet undetermined mechanism, when hyper-activated. Overall, the action of platelets is anti-fibrinolytic, as evidenced by the increase in fibrinolysis associated with reduced platelet number or activity. The plasma expander dextran had no discemable direct effect on platelets, although it did significantly increase the generation of plasmin and the rate of fibrinolysis. This, indirectly, led to a reduction in vWF activity and platelet response to thrombin, but not to TRAP, collagen, or ADP, indicating the these effects result non-specific proteolytic cleavage by plasmin. The contrast media lodixanol or lohexol increased both thrombus formation and resistance to fibrinolysis, whilst Ioxaglate inhibited thrombus formation. These change may in part be due to increased degranulation but is more likely to result from their effect on fibrin fibre formation. These data have implications for clinical resolution of occlusive arterial thrombotic events. Thrombolytic therapy may be more successful if targeted to individuals with lower platelet counts or on long term anti-platelet therapy, and if administered rapidly after thrombus formation. Furthermore low dose Dextran therapy maybe a useful adjuvant to pre-hospital thrombolytic therapy.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available