A New Short Infusion Dosage Regimen of Recombinant Tissue Plasminogen Activator in Patients with Venous Thromboembolic Disease

¹ Scientist of the Medical Research Council of Canada., the Departments of Medicine, and Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
² Scholar of the Heart and Stroke Foundation of Ontario., the Departments of Medicine, and Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
³ The Departments of Medicine, and Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
⁴ Senior Scientist of the Heart and Stroke Foundation of Ontario., the Departments of Medicine, and Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
⁵ Distinguished Professor of the Heart and Stroke Foundation of Ontario., the Departments of Medicine, and Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.

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 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.