Altered fibrin clot properties in patients on long-term haemodialysis: relation to cardiovascular mortality

Abstract

Haemodialysis patients are at an increased risk of cardiovascular (CV) morbidity and mortality. Both end-stage renal disease (ESRD) and thromboembolic coronary events have been shown to be associated with the formation of dense fibrin clots resistant to fibrinolysis. The aim of the present study was to investigate the effect of long-term haemodialysis on clot structure/function and analyse an influence of markers of inflammation, oxidative stress and lipoprotein(a). We sought also to investigate if clot features might be related to CV events and mortality in haemodialysis patients. Subjects and methods. In 33 patients (19 males, 14 females), aged 27 to 89 years, on long-term haemodialysis and 33 age- and sex-matched apparently healthy controls, we investigated fibrin clot properties and susceptibility to lysis using recombinant tissue plasminogen activator by using permeation and turbidity assays. Haemodialysis patients produced fibrin clots that had less porous structure (P < 0.0001) were less susceptible to fibrinolysis (P < 0.0001), began fibrin protofibril formation more quickly (P < 0.0001) and showed increased overall fibre thickness (P < 0.0001) compared with controls. Clot permeability and lysis time correlated with F2-isoprostanes (P < 0.01), Lp(a) (P < 0.0001) and fibrinogen (P < 0.01). None of the clot variables showed associations with the duration of haemodialysis treatment or the cause of ESRD. During a 36-month follow-up, 10 CV deaths were recorded. Mortality was associated with reduced clot permeability (P < 0.0001), prolonged lysis time (P < 0.0001), faster fibrin protofibril formation (P = 0.0004), thicker fibres (P < 0.0001) and increased fibrin clot mass (P < 0.0001). Unfavourably altered clot properties can be detected in haemodialysis patients and may be associated with increased CV mortality.