Fibrinolytic capacity in hemodialysis patients treated with recombinant human erythropoietin.

A major adverse effect of recombinant human erythropoietin (r-HuEPO) in hemodialyzed patients are thrombotic events. Several reports on platelet function during r-HuEPO treatment have been published but less is known about fibrinolysis. In the present study, the fibrinolytic capacity was studied in 20 patients on maintenance hemodialysis and treated with r-HuEPO. The patients were randomized into two groups and investigated in a crossover design. r-HuEPO was administered intravenously and subcutaneously in each group and was given for 3 months, respectively. Plasma tissue plasminogen activator (t-PA) and released t-PA remained unaffected by r-HuEPO in both groups throughout the study. Tissue plasminogen activator inhibitor (PAI) increased in a cyclic way reaching peak values 4-6 weeks after the start of investigation and again 4-6 weeks after changing therapy. The increase in PAI was significant in the two groups (0.025 > p > 0.01). Tissue plasminogen antigen was low in the uremic patients. The influence of r-HuEPO on this parameter was not investigated. Compensatory changes in plasma levels of factor XII procoagulant activity, activated protein C and of alpha 2-antiplasmin were not observed. Thrombotic events occurred in 4 patients at peak values of PAI. Six patients required an increase in heparin dose simultaneously with the increase in PAI. Thus, r-HuEPO seemed to affect the fibrinolytic capacity of uremic patients.