Title:
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Urinary procoagulant activity in health and disease method development and clinical application
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The broad aims of this thesis are to: 1) develop and validate a novel and reliable Urine Tissue Factor (uTF) assay, 2) study uTF function, expression and origin, 3) address factors which might affect uTF measurements in health and renal disorders, 4) re-assess the diagnostic value of uTF levels in cancer, glomerular injuries and inflammatory conditions, 5) examine the hypothesis that uTF levels reflect tumour taken by relating these to disease stage, tumour recurrence and conventional markers of tumour progression and 6) investigate whether uTF levels mirror those of blood mTF activation. Urine and/or blood samples were collected from a total of 1658 subjects covering normal individuals, patients with renal insufficiency, four types of malignant tumours and corresponding benign conditions and glomerulonephritis. The new uTF method is reproducible (intra-assay CV 2.3%, inter-assay CV 8.1%) with very low variation in normal controls and no significant diurnal or day-to-day variation once values were corrected for urine concentration. uTF was expressed on lipid vesicles which are essential for its activity. Cellular TF antigen was localised to the distal and proximal tubules, uTF was stable and levels were not significantly affected by glomerular permeability and filtration, tubular function nor by the presence of contaminants in urine. Patients with malignant tumours, glomerular injury and various inflammatory conditions have significantly higher uTF activity compared to normal subjects or patients with benign non-inflammatory disease. Levels were significantly associated with histological tumour grade, malignant recurrence and other markers of tumour aggressiveness.
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