In vitro studies on hirudin elimination by haemofiltration: comparison of three high-flux membranes.
BACKGROUND
Recombinant hirudin (r-hirudin) is a highly selective thrombin inhibitor used for anticoagulation in heparin-induced thrombocytopenia type II. R-hirudin is increasingly applied to patients with renal failure and on renal replacement therapy. Since kidney function impairment strongly prolongs r-hirudin elimination half-life, severe accumulation and bleeding complications may occur. Data on the r-hirudin permeability and elimination capacity of different haemofilters are limited.


METHODS
Three haemofilter types were investigated: high-flux polysulphone (Fresenius), AN69 (Hospal), and polyamide (Gambro). We used two in vitro haemofiltration models: (i) an open post-dilution haemofiltration model with ultrafiltration and fluid substitution (model 1) simulating hirudin intoxication, and (ii) a closed model with ultrafiltrate reinfusion (model 2) to determine steady-state sieving coefficients (SC). Fresh human heparinized blood (2 IU unfractionated heparin/ml blood) was used. In model 2, SC obtained with human whole blood were compared with isotonic saline.


RESULTS
In model 1, r-hirudin levels decreased significantly faster with polysulphone than with AN69 or polyamide (P<0.05). In accordance with this, in model 2 the observed SC in whole blood were 1.11+/-0.28 (polysulphone), 0.61+/-0.15 (AN69) and 0.33+/-0.13 (polyamide), and clearances were 28+/-7 (polysulphone), 15+/-4 (AN69) and 8+/-3 ml/min (polyamide) (P<0.001 for all comparisons). The SC in saline were slightly but significantly lower for polysulphone (0.88+/-0.12), similar for AN69 (0.59+/-0.1), and significantly improved for polyamide (0.83+/-0.1).


CONCLUSIONS
Elimination of r-hirudin by haemofiltration strongly depended on the membrane material. Using human blood, we observed large differences between the three high-flux membranes. The saline experiments suggest a membrane-dependent impact of plasma proteins and pH on hirudin sieving. Our findings have implications for r-hirudin dosage in haemofiltration, for treatment of overdosage, and for future in vitro haemofiltration studies.
Frank
Rolf Dario
RD
Department of Nephrology and Clinical Immunology, University Hospital Aachen, Germany. dario.frank@ukaachen.de
Farber
Heiko
H
Lanzmich
Regina
R
Floege
Jürgen
J
Kierdorf
Horst Peter
HP
D000328:Adult; D006440:Hemofiltration / Q000295:instrumentation*; D006629:Hirudins / Q000097:blood* / Q000302:isolation & purification*; D006801:Humans; D008567:Membranes, Artificial; D008875:Middle Aged; D012965:Sodium Chloride / Q000737:chemistry
D006629:Hirudins; D008567:Membranes, Artificial; D012965:Sodium Chloride