Summary
The aim of this study was to compare the ability of heparin and recombinant hirudin
(r-hirudin) in preventing accretion of new fibrin on thrombi during and after treatment
with tissue-type plasminogen activator (t-PA) and in enhancing t-PA induced fibrinolysis
in a rabbit jugular vein thrombosis model. Heparin and r-hirudin were infused at doses
capable of doubling aPTT. In the fibrin accretion inhibition experiments t-PA was
infused over 3 h at a dose of 0.2 mg/kg along with saline or heparin, 0.75 mg/ kg
or r-hirudin, 1.25 mg/kg. In rabbits treated with t-PA plus saline, heparin or r-hirudin,
an accumulation of 125I-fibrinogen on the thrombi of 52.5 ±5.1 εg, 49.5 ± 5.6 εg and 23.5 ± 3.5 εg was observed,
respectively, the difference between r-hirudin and both saline and heparin being statistically
significant (p <0.01). The inhibition of fibrin accretion on the thrombi induced by r-hirudin persists
for at least 9 h after the end of the infusion. By that time r-hirudin has been cleared
from the circulation and aPTT has returned to the baseline level for at least 8 h.
t-PA, 0.2, 0.4, and 1 mg/kg, infused with saline produced 34 ± 6%, 52 ± 5% and 79
± 8% lysis of pre-formed thrombi, respectively. The same doses of t-PA infused with
heparin, 0.75 mg/kg, produced 32 ± 3%, 54 ± 5% and 78 ± 6% fibrinolysis, respectively
and infused with r-hirudin, 1.25 mg/kg, 38 ± 3%, 57 ± 5% and 82 ± 8%, respectively.
Thus, no differences in fibrinolysis were observed among the groups of rabbits treated
with heparin, r-hirudin and saline receiving the same dose of t-PA. When thrombolysis
was assessed by thrombus weight treatment with t-PA and r-hirudin was more effective
than treatment with t-PA and saline or heparin. The positive effects of r-hirudin
on t-PA induced thrombolysis we observed deserve to be confirmed in clinical settings.
