A pilot study on primary haemostasis in patients with renal disease

Abstract

Individuals with end stage renal disease (ESRD) are susceptible to both bleeding and thrombotic events due to a compromised coagulation system, especially primary haemostasis. Pathogenesis of such paradox is multifactorial, where bleeding tendencies are thought to arise due to uremic toxins causing haemostatic interferences, whereas thrombotic events are consequential of chronic inflammation and endothelial cell damage. Dialysis is a form of kidney replacement therapy required to remove waste products and toxins. Haemodialysis (HD) and haemodiafiltration (HDF) are two different types of dialysis. Even though one would expect a degree of haemostatic corrections with dialysis, the procedure itself is not only incapable of completely correcting these dysregulations but can also lead to further coagulation imbalances. Assessment of particular sections of the coagulation system can be achieved using several assays in order to determine the presence of both hypo- and hypercoagulable features. These include, platelet aggregometry to assess platelet function and factor assays such as factor XIII (FXIII), fibrinogen, and Von Willebrand Factor (VWF) to identify bleeding or thrombotic risks. Markers of platelet activation and degranulation such as soluble P-Selectin (sP-Selectin) can also provide insight on the state of coagulability. The aforementioned assays were performed on a total of 41 ESRD patients. The results were compared between cohorts undergoing different types of dialysis (HD and HDF) and to 40 controls with preserved kidney function (20 taking aspirin and 20 not taking aspirin). For both HD and HDF, the results were also compared in parallel (pre- vs post-dialysis). Platelet function was impaired with ESRD, even in patients not taking the anti-platelet aspirin. HD and HDF exacerbated platelet aggregation in a similar manner. Clotting factors including fibrinogen and VWF were already significantly elevated pre-dialysis. All clotting factors became significantly elevated post-dialysis. Elevation in FXIII and sP-Selectin was attributed to some physiological effect other than water loss. These results showed a complex disruption of coagulation in uraemia and confirmed a paradoxical risk of bleeding and thrombosis.