Summary
The in vitro anticoagulant activities of recombinant desulphatohirudin (r-hirudin)
were studied in the activated partial thromboplastin time (APTT) and the thrombin
generation test : systems. In the APTT at concentrations below 5 μg/ml, r-hirudin
showed a dose-response curye. At concentrations above 5 μg/ml, the plasma became unclottable,
but in the thrombin generation test , at least 10 μg/ml of r-hirudin was required
for full inhibition of thrombin generation. The antithrombotic effect was assessed
using a rabbit venous stasis model; 150 μg/ml r-hirudin completely prevented thrombus
formation at 10 and 20 min stasis. At antithrombotic dose, the mean bleeding time
ratio measured in a rabbit ear template model, was not prolonged over control values.
At higher doses, the bleeding time ratios were higher than those observed for the
same dosage of heparin. These data indicate that while r-hirudin is an effective antithrombotic
agent, antithrombotic doses have to be carefully titrated to avoid excessive bleeding.
