title: Requirement of heparin for arterial and venous thrombolysis with recombinant tissue-type plasminogen activator.
abstract: The effect of concomitant intravenous (IV) heparin (200 U/kg bolus, followed by 100 U/kg/h) on the efficacy of arterial and venous thrombolysis with IV recombinant tissue-type plasminogen activator (rt-PA; 0.5 mg/kg over 1 hour) was investigated in a combined femoral arterial and venous thrombosis model in the dog. The arterial model consisted of a high-grade stenosis, endothelial damage, and a thrombotic occlusion, and the venous model consisted of a 125I-fibrin-labeled blood clot. After a dose-finding pilot study in four dogs, a randomized, prospective, and blind study was performed in 20 animals pretreated with 2.8 mg/kg IV acetyl salicylic acid (ASA). The combination of rt-PA and heparin (group I, n = 10) induced early (less than 30 minutes) arterial reperfusion in seven dogs, late (greater than 30 minutes) reflow in two dogs, and persistent occlusion in one dog. rt-PA alone (group II, n = 10) was associated with early reperfusion in one dog, late reflow in three dogs, and persistent occlusion in six dogs (P = .018). Reocclusion occurred in five of nine reperfused dogs of group I and in one of four reperfused dogs of group II (P = not significant). Venous clot lysis amounted to 81% +/- 4% (mean +/- SEM) for group I and to 49% +/- 7% for group II (P less than .001). Template bleeding times increased moderately, but significantly, in group I (from 2.2 +/- 0.2 minutes at baseline to 7.0 +/- 1.4 minutes at 30 minutes, P = .006), but only marginally in group II (from 2.2 +/- 0.2 minutes to 3.6 +/- 0.7 minutes, P = .09). No systemic fibrinogen depletion was observed. Thus, the concommitant use of heparin with rt-PA accelerates arterial reperfusion and enhances venous thrombolysis in dogs pretreated with ASA. These results, obtained in a randomized prospective study design, add to a growing body of experimental and clinical evidence, indicating that thrombolytic therapy with rt-PA requires concomitant adjunctive IV heparin for optimal efficacy, even in the face of treatment with ASA.
authors.affiliation: Center for Thrombosis and Vascular Research, University of Leuven, Belgium.
authors.forename: H J
authors.initials: HJ
authors.lastname: Rapold
authors.forename: H R
authors.initials: HR
authors.lastname: Lu
authors.forename: Z M
authors.initials: ZM
authors.lastname: Wu
authors.forename: H
authors.initials: H
authors.lastname: Nijs
authors.forename: D
authors.initials: D
authors.lastname: Collen
mesh_terms: D000818:Animals; D001241:Aspirin / Q000008:administration & dosage; D004285:Dogs; D006493:Heparin / Q000008:administration & dosage*; D011994:Recombinant Proteins; D013924:Thrombophlebitis / Q000628:therapy*; D013927:Thrombosis / Q000628:therapy*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*
chemical_list: D011994:Recombinant Proteins; D006493:Heparin; D010959:Tissue Plasminogen Activator; D001241:Aspirin