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

Objective To compare the efficacy of Yagin(R), a factor Xa inhibitor d erived from the leech Hirudo medicinalis, with those of heparin and hi rudin as adjuncts to recombinant tissue-type plasminogen activator (rT PA) thrombolysis in a rabbit thrombosis model. Methods Thirty-one anim als were allocated randomly to three groups, all administered four bol uses of 0.25 mg/kg rTPA every 10 min for 30 min, 17 mg/kg aspirin intr avenously, and heparin (as a 100 IU/kg bolus followed by infusion of 5 0 IU/kg heparin per h), hirudin (as a 2 mg/kg bolus followed by infusi on of 1 mg/kg hirudin per h), or Yagin (as an 80 mu g/kg bolus followe d by infusion of 43 mu g/kg Yagin per h). Results Administration of Ya gin 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 he parin (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. Conclusions At the indicated single doses, in hibition of factor Xa by a relatively low concentration of Yagin was f ound to be superior than that with either heparin or hirudin for accel erating rTPA thrombolysis.