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.
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.
Agnelli
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G
Istituto di Medicina Interna e Medicina Vascolare, Università di Perugia, Italy. medvasc@unipg.it
Iorio
A
A
Parise
P
P
Goldhaber
S Z
SZ
Levine
M N
MN
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
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