In vitro study of r-hirudin permeability through membranes of different haemodialysers

Background. After introducing the specific thrombin inhibitor recombinant h irudin (r-hirudin) into clinical practice in cases of heparin-induced throm bocytopenia (HIT, type II) the possibility of its use as an anticoagulant d uring haemodialysis treatment in HIT II patients is being discussed more fr equently. On the one hand, the efficient, safe and routine use of r-hirudin during haemodialyses, including the maintenance of a therapeutic blood lev el, presupposes that no r-hirudin will leave the circulation by passing thr ough the dialyser membrane. On the other hand, it is important to have dial ysers whose permeability to r-hirudin allows its efficient removal from the human body because, to date, no antidote is commercially available in case s of dangerously high blood concentrations of r-hirudin. Methods. An in vitro circulation model was used to study the r-hirudin perm eability of some low- and high-flux dialysers. As r-hirudin-containing vehi cles, both albumin-containing saline solution and bovine blood were circula ted in the blood space of the system for 2 h. Transmembrane r-hirudin passa ge was tested by measuring r-hirudin concentration both in the blood and di alysate space fluids using the ecarin clotting time (ECT). Results. Low-flux dialysers with membranes made from polysulfone or regener ated cellulose proved to be almost impermeable to r-hirudin. In contrast, o ther 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 cellul ose membranes proved to be suitable for r-hirudin use in routine haemodialy sis therapy. Other low-flux, and all high-flux, capillaries are permeable t o r-hirudin and offer the possibility of lowering toxic r-hirudin concentra tions after overdosing.