Hirudin elimination by hemofiltration: A comparative in vitro study of different membranes

Background. Recombinant hirudin (r-hirudin) is a highly specific and select ive thrombin inhibitor. Since 1997, it has been approved for the treatment of heparin-induced thrombocytopenia (HIT type II). Renal function impairmen t drastically prolongs the elimination half-life time. In cases of bleeding or overdosage, there is currently no antidote available. Hemofiltration ha s been reported to be useful in r-hirudin elimination. In this study, we de termined sieving coefficients (SCs) and drug clearances for two different h emofilters currently used in clinical medicine and intensive care. Methods. We developed an in vitro postdilution hemofiltration model using 5 00 mi heparinized (2 IU unfractionated heparin/ml) fresh human blood and bi carbonate substitution fluid. The investigated membranes were high-flux pol ysulfone F50 (1.0 m(2), Fresenius) and AN69 Nephral 200 (1.05 m(2), Hospal Cobe). After equilibration, a bolus of Lepirudin was injected into the post filter port to achieve a r-hirudin blood level of approximately 15 mu g/ml. Serial blood and ultrafiltrate samples were taken for the determination of hirudin levels (chromogenic assay) and control parameters. SC and clearanc es were calculated according to standard formulae. Results. The observed SCs and clearances differed significantly between F50 and Nephral 200 (0.60 +/- 0.17 and 21.0 +/- 5.9 ml/min, respectively, vs. 0.44 +/- 0.09 and 15.5 +/- 3.0 ml/min, respectively; P = 0.001). The determ ination of prothrombin fragments showed no coagulation activation during th e experiments. The hematocrit values remained stable. Conclusions. Our data show that r-hirudin can be eliminated by hemofiltrati on. The elimination obviously depends on the membrane material with high-fl ux polysulfone being more effective than AN69. These findings may be import ant in cases of overdosage and for r-hirudin dosage guidelines in continuou s hemofiltration.