Bolus Thrombolysis in Venous Thromboembolism

¹ The Istituto di Medicina Interna e Medicina Vascolare, Università di Perugia, Perugia, Italy.

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. SEE FIGURE 8 in SOURCE PDF

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.

Thus, our studies confirmed the efficacy of the rt-PA bolus, but they also showed that the standard therapeutic approach has to be improved. More effective concomitant adjunctive treatment and use of a plasminogen activator with a prolonged half-life appear, at present, to be promising approaches. The definite role of these emerging strategies will depend on their clinical efficacy and safety, with bleeding side effects being the main concern.