title: 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.
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: M N
authors.initials: MN
authors.lastname: Levine
authors.forename: J
authors.initials: J
authors.lastname: Weitz
authors.forename: A G
authors.initials: AG
authors.lastname: Turpie
authors.forename: M
authors.initials: M
authors.lastname: Andrew
authors.forename: M
authors.initials: M
authors.lastname: Cruickshank
authors.forename: J
authors.initials: J
authors.lastname: Hirsh
mesh_terms: D001367:Axillary Vein; D001780:Blood Coagulation Tests; D006801:Humans; D007275:Injections, Intravenous; D011655:Pulmonary Embolism / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D011877:Radionuclide Imaging; D011994:Recombinant Proteins; D013350:Subclavian Vein; D015912:Thrombolytic Therapy; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator