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

Abstract

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.

Hemofiltration of Recombinant Hirudin by Different Hemodialyzer Membranes

“…Comparable SC were recently reported for PS and PA high-flux hemodialyzer membranes in a similar setup, albeit at markedly higher hirudin concentrations (15 to 18 g/ml) based on an in vitro circulation period of 30 min (13). A recent study determined so-called hirudin permeability factors of 19 hemodialyzer membranes in vitro (10). The in vitro setup, which did not allow for constant filtrate flow because of sealing of the filtrate space, the hirudin concentrations applied (30 to 50 g/ml, far beyond the clinically suitable range), and the way hirudin permeability was determined (only two pairs of hirudin concentration blood/ filtrate per hemodialyzer), render the direct transfer of the respective results to clinical hemofiltration difficult.…”

“…The experimental design did not allow determination of SC according to standard methods. However, all high-flux hemodialyzer membranes tested showed significant hirudin permeability (10).…”

“…It has been reported that some low-flux hemodialyzers allow for hirudin filtration as well (10,11). For this reason, we additionally investigated four low-flux hemodialyzer membranes.…”

Tackling the Devastating Effects of Heparin‐Induced Thrombocytopenia

“…In vitro, lowflux dialyzers have been shown to be only partially permeable or impermeable, whereas high-flux dialyzers were permeable to lepirudin. 11,12 In vivo, using intermittent hemodialysis, however, lepirudin elimination was not enhanced by the use of highflux dialyzers. 5 Hemofiltration using continuous renal replacement therapy with continuous venovenous hemofiltration/dialysis with high-flux dialyzers has been shown to enhance lepirudin removal requiring increased dosages for maintenance of adequate anticoagulation.…”

“…10 Use of continuous hemofiltration with high-flux dialyzers has been advocated in lepirudin overdose situations. 11 We initiated therapy at the lower range of doses reported by Vanholder et al 5 of 0.025 mg/kg following an initial bolus dose of 0.1 mg/kg. Our decision was based on: 1) inability to reverse anticoagulant effects (no antidote, questionable removal with hemodialysis); and 2) increased risk of major bleeding (liver dysfunction and other comorbidities).…”