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, 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.


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Kornowski
R
R
Department of Cardiology, Sourasky' Medical Center, Ichilbv Hospital, Tel-Aviv, Israel.
Eldor
A
A
Werber
M M
MM
Ezov
N
N
Zwang
E
E
Nimrod
A
A
Chernine
A
A
Finkelstein
A
A
Panet
A
A
Laniado
S
S
Keren
G
G
D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D000991:Antithrombins / Q000627:therapeutic use*; D004195:Disease Models, Animal; D065427:Factor Xa Inhibitors; D006493:Heparin / Q000627:therapeutic use*; D024764:Hirudin Therapy; D007865:Leeches; D015425:Myocardial Reperfusion; D010314:Partial Thromboplastin Time; D011817:Rabbits; D011994:Recombinant Proteins / Q000627:therapeutic use; D015912:Thrombolytic Therapy; D013927:Thrombosis / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D014654:Vascular Patency
D000925:Anticoagulants; D000991:Antithrombins; D065427:Factor Xa Inhibitors; D011994:Recombinant Proteins; D006493:Heparin; D010959:Tissue Plasminogen Activator