Recombinant hirudin: a specific thrombin inhibiting anticoagulant for hemodialysis.
The first experience with hirudin as an alternative anticoagulant for heparin in hemodialysis is reported. Recombinant hirudin (HBW 023) was administered in 20 patients as a bolus before dialysis with low flux polysulfone dialyzers (PS400), the dosage being adapted stepwise from patient to patient by 0.02 mg/kg to the occurrence of clotting or bleeding. Four different administration schedules were studied. The first three schedules (0.02 mg/kg, N = 1; 0.04 mg/kg, N = 1; 0.06 mg/kg, N = 4) were discontinued because of clotting. The 0.08 mg/kg schedule was maintained without clotting event in 14 patients. Bleeding was not observed. Plasma hirudin averaged 503.9 +/- 214.0 and 527.7 +/- 217.1 ng/ml after two and four hours of dialysis, and decreased during an interdialytic interval of 44 hours to 223.2 +/- 86.2 ng/ml. Modified antithrombin III (P < 0.05) and activated partial thromboplastin times were lower (P < 0.01) under hirudin compared to heparin; these coagulation parameters were closer to normal during hirudin treatment. The patients developing clotting could be distinguished from those without clotting by the registration of the activated clotting times (9.2 +/- 3.0 vs. 18.7 +/- 3.2 min after 2 hr, P < 0.01; 8.1 +/- 3.0 vs. 16.2 +/- 3.8 min after 4 hr of dialysis, P < 0.05); cut-off value below which clotting is to be expected was 12 min). It is concluded that administration of hirudin as a bolus before the start of dialysis, at a dosage of 0.08 mg/kg, is not complicated by clotting or by bleeding. Coagulation tendency can optimally be monitored by the registration of the activated clotting time.(ABSTRACT TRUNCATED AT 250 WORDS)
Vanholder
R C
RC
Nephrology Department, University Hospital, Ghent, Belgium.
Camez
A A
AA
Veys
N M
NM
Soria
J
J
Mirshahi
M
M
Soria
C
C
Ringoir
S
S
D000328:Adult; D000368:Aged; D004334:Drug Administration Schedule; D005260:Female; D006493:Heparin / Q000627:therapeutic use; D024764:Hirudin Therapy; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use; D006435:Renal Dialysis; D013917:Thrombin / Q000037:antagonists & inhibitors*; D013927:Thrombosis / Q000517:prevention & control*
D011994:Recombinant Proteins; D006493:Heparin; D013917:Thrombin