Haemostasis in progressive renal failure

This thesis describes a series of clinical and haematological studies of patients with chronic renal failure. My aim was to investigate the role of haemostatic abnormality in two aspects of renal disease: (1) The bleeding tendency of uraemia. (2) The progression of renal failure. (1) In the first part of the thesis I show that anaemia appears to be the most important determinant of uraemic bleeding. The development of a prolonged bleeding time in the early stages of renal failure was documented, and experiments were performed to identify platelet functional abnormalities which might develop in parallel, and hence explain the haemorrhagic defect. The only significant relationship which emerged was a negative correlation between the haematocrit and the bleeding time. This was further investigated by studying platelet function during correction of anaemia with recombinant human erythropoietin. Bleeding time was shortened following erythropoietin, by a degree which correlated with the increase in the haematocrit, but not with any changes in platelet reactivity. A study of platelet aggregation in whole blood showed an aggregation-enhancing effect of uraemic red cells which was not evident with normal erythrocytes. (2) In the second part of the thesis, increased blood viscosity and intravascular haemostatic activation were demonstrated in both diabetic and non-diabetic patients with progressive renal disease, abnormalities which might promote non-immune glomerular injury and hence the progression of renal failure. It was not clear, however, whether these changes represented cause or effect of disease, since in multiple regression analysis, proteinuria emerged as the major independent determinant of progression. A clinical study of antiplatelet therapy in progressive renal failure showed a slowing of progression in half the patients treated, and, in diabetic nephropathy, a significant reduction in proteinuria. These results suggest a partial role for haemostasis in the progression of renal injury