Recombinant tissue plasminogen activator for the treatment of lower extremity peripheral vascular occlusive disease

Regional thrombolysis in the recanalization of peripheral vascular occlusive disease is an increasingly accepted therapeutic modality. Efficacy and complication rate are major issues in thrombolytic therapy. This prospective study was undertaken to determine if locally delivered recombinant tissue plasminogen activator (r-TPA) is safe and effective in clot lysis at non-weight-adjusted doses.

Twenty patients (undergoing 21 infusions) from two centers underwent fibrinolytic therapy with use of r-TPA, at a dose rate of 2 mg/h. The mean duration of arterial occlusion was 27.2 days (range, 1-117 days). Concomitant intravenous heparin anticoagulation was administered to all patients. A coaxial infusion delivery system was employed. Hematologic parameters and angiographic follow-up were evaluated at 4-hour intervals during thrombolytic infusion. The chosen maximum r-TPA dose of 40 mg could be extended at investigator discretion.

Complete clot lysis was achieved in 18 of 21 (85.7%) infusions at a mean total dose of 38.9 mg (range, 8-84 mg). The mean infusion duration was 19.7 hours. In 16 of 19 (84.2%) infusions, in which the nadir fibrinogen level was recorded, it remained greater than 65% of baseline. Three of 21 (14.3%) infusions resulted in three major bleeding complications, one of which resulted in death.

In this two-center trial, catheter-directed r-TPA infusion at 2 mg/h is effective for clot lysis. When combined with concomitant heparin administration, this treatment may result in an unacceptably high frequency of bleeding complications.