title: Pharmacodynamics of thrombolysis with recombinant tissue-type plasminogen activator. Correlation with characteristics of and clinical outcomes in patients with acute myocardial infarction. The TAMI Study Group.
abstract: Coagulation analysis was performed on blood samples from 386 patients with acute myocardial infarction drawn before, during, and after a continuous intravenous infusion of 150 mg recombinant tissue-type plasminogen activator (rt-PA) (Activase). Plasma rt-PA rose to peak levels of 2.1 +/- 3.1 micrograms/ml (mean +/- SD). Fibrinogen levels measured by coagulation rate and by sulfite precipitation decreased from baseline levels of 3.0 +/- 0.9 and 3.2 +/- 1.0 g/l, respectively, to nadir levels of 1.4 +/- 0.75 and 1.8 +/- 0.92 g/l, respectively, and were associated with peak levels in serum of fibrinogen-degradation products (FDP) of 230 +/- 470 micrograms/ml. Forty percent of patients experienced a nadir functional-fibrinogen level of less than 1.0 g/l, whereas 20% fell below 0.5 g/l. Nadir fibrinogen levels did not correlate with patency of the infarct-related coronary artery at 90 minutes or with risk of coronary vessel reocclusion within 7-10 days. However, the risk of coronary artery reocclusion was inversely related to the baseline functional fibrinogen level (p = 0.0008), with the magnitude of its drop to nadir level (p = 0.0003) as well as to peak levels of FDP (p = 0.038). Quantitative blood loss correlated with all markers for systemic fibrinogenolysis including nadir fibrinogen level (r = -0.20, p = 0.0011), percent decrease of fibrinogen (r = 0.22, p = 0.001), and peak FDP levels (r = 0.14, p = 0.020). Both patients who experienced intracranial hemorrhage presented with high baseline fibrinogen levels and experienced extensive degradation of coagulable fibrinogen. Overall, patients at greatest risk of systemic fibrinogenolysis tended to be relatively older women with lower body weight.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, University of Vermont, College of Medicine, Burlington.
authors.forename: D C
authors.initials: DC
authors.lastname: Stump
authors.forename: R M
authors.initials: RM
authors.lastname: Califf
authors.forename: E J
authors.initials: EJ
authors.lastname: Topol
authors.forename: K
authors.initials: K
authors.lastname: Sigmon
authors.forename: D
authors.initials: D
authors.lastname: Thornton
authors.forename: R
authors.initials: R
authors.lastname: Masek
authors.forename: L
authors.initials: L
authors.lastname: Anderson
authors.forename: D
authors.initials: D
authors.lastname: Collen
mesh_terms: D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D005340:Fibrinogen / Q000187:drug effects; D006801:Humans; D009203:Myocardial Infarction / Q000188:drug therapy*; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D005340:Fibrinogen; D010959:Tissue Plasminogen Activator