The results of the study are shown in Figure 8. Three hours after rt-PA bolus, 56 ± 7 |xg of radioactive fibrin had accreted on the thrombi. This amount was reduced to 24 ± 3 |xg 3 h after a bolus of K2tu-PA. The difference between rt-PA and Kgtu-PA was statistically significant (p<0.01). These results seem to indicate that prolonging plasminogen half-life results in an effective prevention of accretion of new fibrin on the thrombi. In considering the value of this observation, one has to take into account other aspects of thrombolytic therapy, including bleeding side effects.
The series of experimental studies we have described in this article provide the following information:
1. Bolus rt-PA is an effective thrombolytic regimen, since it efficiently reduces thrombus size.
2. As with rt-PA infusion, a marked accretion of new fibrin on the thrombus is observed after bolus rt-PA administration.
3. “Therapeutic” doses of heparin are not effective in preventing the accretion of new fibrin on the thrombi after rt-PA bolus; much higher doses, hardly ever used in humans, are necessary.
4. Hirudin given at doses able to double aPTT is effective in inhibiting accretion of new fibrin on the thrombi after a bolus of rt-PA.
5. Administration of a bolus of K2tu-PA, a hybrid plasminogen activator with prolonged half-life, is followed by a lower accretion of new fibrin on the thrombi than that achieved with a bolus of rt-PA.
Figure 8. Accretion of new fibrin on preexisting thrombi during 3 h following bolus injection of rt-PA or Katu-PA.