In vitro study of r-hirudin permeability through membranes of different haemodialysers.
BACKGROUND
After introducing the specific thrombin inhibitor recombinant hirudin (r-hirudin) into clinical practice in cases of heparin-induced thrombocytopenia (HIT, type II) the possibility of its use as an anticoagulant during haemodialysis treatment in HIT II patients is being discussed more frequently. On the one hand, the efficient, safe and routine use of r-hirudin during haemodialyses, including the maintenance of a therapeutic blood level, presupposes that no r-hirudin will leave the circulation by passing through the dialyser membrane. On the other hand, it is important to have dialysers whose permeability to r-hirudin allows its efficient removal from the human body because, to date, no antidote is commercially available in cases of dangerously high blood concentrations of r-hirudin.


METHODS
An in vitro circulation model was used to study the r-hirudin permeability of some low- and high-flux dialysers. As r-hirudin-containing vehicles, both albumin-containing saline solution and bovine blood were circulated in the blood space of the system for 2 h. Transmembrane r-hirudin passage was tested by measuring r-hirudin concentration both in the blood and dialysate space fluids using the ecarin clotting time (ECT).


RESULTS
Low-flux dialysers with membranes made from polysulfone or regenerated cellulose proved to be almost impermeable to r-hirudin. In contrast, other low-flux membranes were partly permeable to r-hirudin (e.g. Hemophan) or even almost completely permeable (e.g. cellulose acetate). All high-flux dialysers tested were permeable to r-hirudin.


CONCLUSIONS
Only low-flux dialysers with polysulfone or regenerated cellulose membranes proved to be suitable for r-hirudin use in routine haemodialysis therapy. Other low-flux, and all high-flux, capillaries are permeable to r-hirudin and offer the possibility of lowering toxic r-hirudin concentrations after overdosing.
Bucha
E
E
Max-Planck-Gesellschaft, Research Unit Pharmacological Haemostaseology, Friedrich-Schiller-University, Jena, Germany.
Kreml
R
R
Nowak
G
G
D006629:Hirudins / Q000493:pharmacokinetics*; D006801:Humans; D008567:Membranes, Artificial; D010539:Permeability; D011994:Recombinant Proteins / Q000493:pharmacokinetics; D006435:Renal Dialysis
D006629:Hirudins; D008567:Membranes, Artificial; D011994:Recombinant Proteins