title: Fibrinogenolysis and thrombin generation after reduced dose bolus or conventional rt-PA for pulmonary embolism. The Coagulation Project Investigators of the Bolus Alteplase Pulmonary Embolism Group.
abstract: The aim of this study was to compare the effects on fibrinogenolysis and thrombin generation of two recombinant tissue-type plasminogen activator (rt-PA) regimens in patients with pulmonary embolism entering a randomised, controlled study with a 1:2 allocation ratio to rt-PA, 100 mg over 2 h (Group A) or rt-PA, 0.6 mg/kg, maximum dose 50 mg, over 15 min (Group B). In both groups the heparin infusion was stopped 2-4 h before starting thrombolytic treatment and resumed accordingly to the activated partial thromboplastin time (aPTT) or thrombin clotting time (TcT). Seventeen patients in Group A and 30 patients in Group B were evaluated before starting thrombolytic treatment and 2, 6 and 24 h after its end for the following parameters: aPTT, TcT, fibrinogen, fibrinogen degradation products (FDP), plasmin-alpha 2 antiplasmin (PAP) and thrombin-antithrombin III (TAT) complexes. The two groups had similar coagulation parameters at baseline. Two h after starting rt-PA, the aPTT was more prolonged in Group A than in Group B patients (P = 0.01). Patients in Group B showed less reduction in plasma fibrinogen levels at all study times after rt-PA treatment (P = 0.008). The increase in plasma FDP (P = 0.037) and PAP (P = 0.001) levels was lower at 2 and 6 h samples in Group B compared with Group A. TcT was prolonged (P = 0.003) and TAT increased (P = 0.001) during treatment without differences between the two groups. AUC0-24 of fibrinogen, FDP and PAP levels confirmed the statistically significant differences (P = 0.04) between the two groups over the entire 24 h period of the study. Three patients in Group A (17.6%) and three (10.0%) in Group B suffered major or other important bleeding. Our results indicate that the administration of weight-adjusted reduced-dose rt-PA bolus produces less impairment of blood coagulation than the FDA approved regimen.
authors.affiliation: Istituto di Medicina Interna e Medicina Vascolare, Università di Perugia, Italy. medvasc@unipg.it
authors.forename: G
authors.initials: G
authors.lastname: Agnelli
authors.forename: A
authors.initials: A
authors.lastname: Iorio
authors.forename: P
authors.initials: P
authors.lastname: Parise
authors.forename: S Z
authors.initials: SZ
authors.lastname: Goldhaber
authors.forename: M N
authors.initials: MN
authors.lastname: Levine
mesh_terms: D000328:Adult; D000933:Antifibrinolytic Agents / Q000378:metabolism; D000990:Antithrombin III / Q000378:metabolism; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism*; D005341:Fibrinolysin / Q000378:metabolism; D005342:Fibrinolysis; D006801:Humans; D010314:Partial Thromboplastin Time; D010447:Peptide Hydrolases / Q000378:metabolism; D010960:Plasminogen Activators / Q000627:therapeutic use*; D011655:Pulmonary Embolism / Q000097:blood / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use; D013917:Thrombin / Q000096:biosynthesis*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*; D000979:alpha-2-Antiplasmin
chemical_list: D000933:Antifibrinolytic Agents; D005338:Fibrin Fibrinogen Degradation Products; D011994:Recombinant Proteins; D000979:alpha-2-Antiplasmin; C046193:antithrombin III-protease complex; C037742:plasmin-plasmin inhibitor complex; D000990:Antithrombin III; D005340:Fibrinogen; D010447:Peptide Hydrolases; D010960:Plasminogen Activators; D013917:Thrombin; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin