Fibrinokinetic Deficit in Chronic Kidney Disease and End Stage Renal Disease Patients Contributes to the Hemostatic Abnormalities

Abstract

An increase in bleeding is observed in patients with chronic kidney disease (CKD) and end stage renal disease (ESRD) despite the normal coagulation profile and fibrinogen level. The hemostatic deficit in these patients may due to the defects in fibrin formation. The fibrinokinetic profile of CKD (n=50) and ESRD patients on hemodialysis prior to and after dialysis was measured. Citrated plasma from each patient was supplemented with 25 μl of 5 U thrombin and 25 μl of 0.05 M CaCl. The rate of fibrin formation was measured by monitoring the optical density (OD) at 405 nM. After reaching steady state, 50 μl of urokinase (30,000 U/ml) was added to measure the fibrinolytic profile. Forty normal male and female individuals were also analyzed. In addition PT, aPTT and fibrinogen levels were also measured. The normal male and female fibrinokinetic profile showed a strong clot formation with the clot reaching an average OD of 1.2±0.3 (range 0.7–1.4). In the CKD patients a much weaker clot was formed with an average OD of 0.21±0.13 (range 0.05–0.41). In the ESRD patients on maintenance hemodialysis, the pre-dialysis sample showed a weaker fibrinokinetic profile reaching near normal levels with a clot density of 1.3±0.4 (range 0.8–1.6). In the urokinase induced fibrinolysis assay, the CKD patients plasma exhibited a much stronger fibrinolytic index in comparison to the normal population (80% clot lysis vs. 20%). In the ESRD patients the clot lysis profile was relatively weaker in comparison to the CKD patients, suggesting that hemodialysis may contribute to impaired clot formation. These results are contrary to the reported observations that dense clot resistant to fibrinolysis are formed in CKD and ESRD patients. Furthermore the clot sobserved in these patients were highly susceptible to lysis. The maintenance hemodialysis results in improving the fibrinokinetic and fibrinolytic profile in the ESRD patients. Therefore maintenance hemodialysis contributes to improved hemostasis in ESRD patients.