Enhancement of recombinant tissue-type plasminogen activator thrombolysis with a selective factor Xa inhibitor derived from the leech Hirudo medicinalis: comparison with heparin and hirudin in a rabbit thrombosis model

To compare the efficacy of Yagin, a factor Xa inhibitor derived from the leech Hirudo medicinalis, with those of heparin and hirudin as adjuncts to recombinant tissue-type plasminogen activator (rTPA) thrombolysis in a rabbit thrombosis model. Thirty-one animals were allocated randomly to three groups, all administered four boluses of 0.25 mg/kg rTPA every 10 min for 30 min, 17 mg/kg aspirin intravenously, and heparin (as a 100 IU/kg bolus followed by infusion of 50 IU/kg heparin per h), hirudin (as a 2 mg/kg bolus followed by infusion of 1 mg/kg hirudin per h), or Yagin (as an 80 micrograms/kg bolus followed by infusion of 43 micrograms/kg Yagin per h). Administration of Yagin was associated with a significant acceleration of the reflow time, this time being 14.5 +/- 1.2 min with Yagin, 25.8 +/- 5.2 min with heparin (P < 0.0001, versus Yagin), and 28.7 +/- 16.0 min with hirudin (P = 0.012, versus Yagin). Overall patency did not differ significantly among the three groups. At the indicated single doses, inhibition of factor Xa by a relatively low concentration of Yagin was found to be superior than that with either heparin or hirudin for accelerating rTPA thrombolysis.