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.
Aunsholt
N A
NA
Department of Medicine C, Aalborg Hospital, Denmark.
Ahlbom
G
G
Steffensen
G
G
Glud
T
T
D000328:Adult; D000368:Aged; D004921:Erythropoietin / Q000627:therapeutic use*; D005340:Fibrinogen / Q000378:metabolism; D005342:Fibrinolysis; D006801:Humans; D007676:Kidney Failure, Chronic / Q000628:therapy*; D008875:Middle Aged; D015849:Plasminogen Inactivators / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use; D006435:Renal Dialysis / Q000379:methods*; D010959:Tissue Plasminogen Activator / Q000378:metabolism
D015849:Plasminogen Inactivators; D011994:Recombinant Proteins; D004921:Erythropoietin; D005340:Fibrinogen; D010959:Tissue Plasminogen Activator