Abstract

Background. Patients with advanced CRF evolve with subclinical activation of hemostasis. as evidenced by increased plasma markers of thrombin and plasmin production (Mezzano D. et al, Thromb Haemostas 1996; 76:312). Hemostatic activation correlates with signs of endothelial cell activation and dysfunction (Thromb Res, in press). Defects of this nature are frequently found in patients with systemic inflammation. Our aim was to detect signs of systemic inflammatory reaction in CRF and to study their association with hemostatic and endothelium defects. Methods. TNF-a (Elisa), C-reactive protein (CRP) (Elisa), fibrinogen (Fg) (Klauss) were measured in fasting blood samples obtained from 60 patients before initiating hemodialysis treatment (plasma creatinine 6.06±3.6 mg/dL, hematocrit 30±5.6%, without diabetes mellitus. active inflammatory diseases or drugs affecting hemostasis). Results were compared with 12 healthy controls and correlated with endothelial cell markers and with indices of activation of coagulation and fibrholysis. Results. TNFa, CRP and Fg in patients (38.7±23.2 pg/mL, 4.6±6.9 mg/L and 586 mg/dL) were significantly higher (p=0.001, p < 0.0001 and p < 0.0001) than in controls (20.5± 12.3 pg/mL, 0.36±0.27 mg/L and 248± 32). Plasma CRP was above the normal range in 65% of patients. These inflammatory markers were significantly correlated among them, with plasma creatinine level and with activation markers of endothelium, coagulation and fibrinolysis. For example, correlation coefficients of CRP with von Willebrand factor (r=0.50), prothrombin fragment 1+2 (r=0.40), plasmin-antiplasmin complexes (r=0.45) and fibrin degradation products (r=0.33) were statistically significant (p at least 0.01). Conclusion. Increased generation of inflammatory cytokines in CRF may explain a mild, chronic systemic inflammatory response, endothelial cell dysfunction and compensated, subclinical activation of coagulation and fibrinolysis. (Fondecyt 1971048).