A new short infusion dosage regimen of recombinant tissue plasminogen activator in patients with venous thromboembolic disease

Abstract

Although recombinant tissue-type plasminogen activator (rt-PA) has the potential to induce thrombolysis without producing a generalized coagulopathy, the dosage regimens in present use induce a plasma fibrinolytic state and are associated with bleeding. Animal experiments have demonstrated that rt-PA produces continuing thrombolysis after it is cleared from the circulation and that thrombolysis is increased and bleeding is reduced when rt-PA is administered over a short time period. To determine whether a short course regimen of rt-PA has potential in man, we gave a bolus injection of rt-PA (0.6 mg/kg) concurrently with heparin to five patients with venous thromboembolism. Three patients with angiographically proven pulmonary embolism had marked improvement of the perfusion defects when lung scans were repeated 24 h after rt-PA administration. In one of two patients with thrombosis of the deep veins of the upper extremity the venographic defect resolved completely. In three of four patients there was a mild decrease in fibrinogen and a moderate decrease in alpha 2-antiplasmin levels. There was no excessive bleeding. These results suggest that a bolus injection regimen of rt-PA has considerable potential in the treatment of thromboembolic disease.