| dc.description.abstract | End stage kidney disease is associated with an increased risk of both bleeding and clotting. Patients receiving haemodialysis have excess morbidity and mortality from major bleeding, as well as cardiovascular events. During haemodialysis the use of systemic anticoagulation is required to prevent clotting of the extracorporeal circuit. The contribution of this to major bleeding events is unknown. There are two main types of anticoagulation: unfractionated heparin and low molecular weight heparins. There is little data directly comparing these agents, guiding their dosing or monitoring. There is controversy about the development of anti-platelet factor4 antibodies in haemodialysis patients which may impact on cardiovascular risk. This thesis aimed to (1) describe in detail the coagulation profile of patients undergoing haemodialysis, specifically identifying differences between unfractionated and low molecular weight heparin, (2) ascertain the utility of Thrombin Generation and ROTEM in dialysis-requiring end-stage kidney disease, (3) investigate the prevalence of anti-PF4 antibodies in patients dialysed with different haemodialysis anticoagulants, and (4) investigate whether a point-of-care test, such as ROTEM, would confer benefit in predicting the bleeding phenotype. 120 patients were studied across two hospital sites; Southend Hospital where unfractionated heparin was used as dialysis anticoagulant, and Royal London Hospital where low molecular weight heparin was used. Patients were studied on a single haemodialysis session at 4 time points. TG decreased at the end of dialysis in both cohorts but significantly more in the unfractionated heparin group. This was not easily correlated with standard clotting tests, anti-IIa or anti-Xa results. ROTEM parameters were abnormal at the end of dialysis and partially associated with standard tests of clotting, but not with TG results. Standard ROTEM reagents were not useful for assessing the LMWH affect, but kaolin and PiCT both showed promise as novel reagents. HIT antibodies were not found in either cohort of patients. | en_US |
