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

Abstract

Background: Recombinant hirudin (r-hirudin) is a highly specific and selective thrombin inhibitor. Since 1997, it has been approved for the treatment of heparin-induced thrombocytopenia (HIT type II). Renal function impairment drastically prolongs the elimination half-life time. In cases of bleeding or overdosage, there is currently no antidote available. Hemofiltration has been reported to be useful in r-hirudin elimination. In this study, we determined sieving coefficients (SCs) and drug clearances for two different hemofilters currently used in clinical medicine and intensive care.

Methods: We developed an in vitro postdilution hemofiltration model using 500 ml heparinized (2 IU unfractionated heparin/ml) fresh human blood and bicarbonate substitution fluid. The investigated membranes were high-flux polysulfone F50 (1.0 m2, Fresenius) and AN69 Nephral 200 (1.05 m2, Hospal Cobe). After equilibration, a bolus of Lepirudin was injected into the postfilter port to achieve a r-hirudin blood level of approximately 15 microg/ml. Serial blood and ultrafiltrate samples were taken for the determination of hirudin levels (chromogenic assay) and control parameters. SC and clearances 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 determination of prothrombin fragments showed no coagulation activation during the experiments. The hematocrit values remained stable.

Conclusions: Our data show that r-hirudin can be eliminated by hemofiltration. The elimination obviously depends on the membrane material with high-flux polysulfone being more effective than AN69. These findings may be important in cases of overdosage and for r-hirudin dosage guidelines in continuous hemofiltration.