Hemofiltration of recombinant hirudin by different hemodialyzer membranes: implications for clinical use

Recombinant hirudin (lepirudin) is a potent direct thrombin inhibitor that is used particularly for treatment of immune-mediated heparin-induced thrombocytopenia. Because hirudin is almost exclusively eliminated by the kidneys, its half-life is markedly prolonged in patients with severe renal insufficiency. Therefore, these patients are at risk for bleeding, particularly because no antidote is available. To use hirudin safely in patients who are on renal replacement therapy, knowledge of hirudin-sieving characteristics of different hemodialyzers is required. Data on this issue are sparse and in part contradictory. Eight different conventional low-flux and high-flux hemodialyzers were tested in an in vitro circuit with ultrafiltrate reinfusion. In each experiment, lepirudin concentration was repetitively measured during 3 h in the prefilter, the postfilter, and the filtration line using a chromogenic assay. On the basis of these data, sieving coefficients were calculated. All high-flux hemodialyzers tested allowed filtration of hirudin yet with marked differences in steady-state sieving (sieving coefficients in whole blood: polysulfone [PS] 0.97 +/- 0.03; polymethylmethacrylate [PMMA] 0.75 +/- 0.02; polyarylethersulfone 0.73 +/- 0.02; polyamide 0.49 +/- 0.02). None of the low-flux hemodialyzer membranes tested (cuprophane, hemophane, PS, and PMMA) showed significant hirudin filtration. Owing to marked differences in hirudin-sieving characteristics, choice of the appropriate hemodialyzer membrane is an important determinant of bleeding risk in dialysis-dependent patients who are treated with hirudin. In case of overdosage or bleeding complications, hemofiltration via PS membranes is recommended to reduce plasma hirudin concentration. Hirudin dosage should be adapted not only to the clinical situation but also to the hirudin-sieving characteristics of the assigned dialyzer.