The effect of r-hirudin vs. heparin on blood-membrane interactions during hemodialysis.
The aim of this study was to determine if recombinant (r-)hirudin, used as anticoagulant during hemodialysis, has favourable effects on blood-membrane interactions. The results were compared with that obtained when standard unfractionated heparin, the anticoagulant of choice, was used.


METHODS
Eleven patients with chronic renal failure and on maintenance hemodialysis were included in this open cross-over study. Heparin was administered according to the existing protocol in use at the Dialysis Unit during the first dialysis of the study (5,000 to 10,000 IU). r-Hirudin, 0.15 mg/kg, was given as a bolus at the start of the second dialysis, two days later. The effect of the anticoagulant on leukocyte and complement activation, thrombogenesis, release of platelet activating factor and pulmonary gas exchange was studied.


RESULTS
In most cases after dialysis with heparin (8 of 11), but not with r-hirudin, macroscopically visible thrombi formed at the inlet of the artificial kidneys. Irrespective of the anticoagulant used, a transient leukopenia (neutropenia) developed ten minutes after dialysis was started. Heparin anticoagulation resulted in a significant increase in plasma levels of complement C3a at all time points, whereas with r-hirudin the increase was significant after only 30 and 240 min. The O2 saturation decreased significantly during the first two hours of dialysis with heparin. The partial O2 pressure decreased significantly during the first two hours of dialysis, irrespective of the anticoagulant used.


CONCLUSIONS
We conclude that r-hirudin is superior to heparin with regard to inhibition of thrombus formation in the dialyzer during hemodialysis. Slight, but favourable effects on complement activation. O2 saturation and lung CO diffusing capacity were also found with r-hirudin.
van Wyk
V
V
Department of Hematology, University of the Free State, Bloemfontein, South Africa.
Badenhorst
P N
PN
Kotzé
H F
HF
D000328:Adult; D000925:Anticoagulants / Q000494:pharmacology*; D001769:Blood / Q000187:drug effects*; D003167:Complement Activation / Q000187:drug effects; D006493:Heparin / Q000494:pharmacology*; D006629:Hirudins / Q000494:pharmacology*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000628:therapy; D007688:Kidneys, Artificial; D007962:Leukocytes / Q000187:drug effects; D008567:Membranes, Artificial; D008875:Middle Aged; D011480:Protease Inhibitors / Q000494:pharmacology*; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D006435:Renal Dialysis / Q000295:instrumentation
D000925:Anticoagulants; D006629:Hirudins; D008567:Membranes, Artificial; D011480:Protease Inhibitors; D006493:Heparin