title: Thrombin generation, inhibition and clinical outcomes in patients with acute myocardial infarction treated with thrombolytic therapy and heparin: results from the GUSTO-I Trial. GUSTO-I Hemostasis Substudy Group. Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries.
abstract: OBJECTIVE
  We sought to assess the effects of antithrombotic therapy after thrombolysis for acute myocardial infarction on markers of thrombin generation and activity and to determine the relation of these markers with clinical outcomes.
  
  
  BACKGROUND
  Thrombin activation and generation often occur with thrombolysis for acute myocardial infarction. Antithrombotic regimens have been developed to reduce the resulting thrombotic complications.
  
  
  METHODS
  We sampled plasma markers of thrombin generation and activity after thrombolysis in 292 patients. We assessed the relations of these markers with clinical outcomes at 30 days.
  
  
  RESULTS
  Fibrinopeptide A (FPA), a marker of thrombin activity toward fibrinogen, was elevated at baseline (12.3 ng/ml) and increased to 18.4 ng/ml by 90 min after streptokinase and subcutaneous heparin treatment. With intravenous heparin, this increase was attenuated, but intravenous heparin did not prevent thrombin generation, as measured by prothrombin fragment 1.2 (F1.2). Heparin level, measured by anti-Xa activity, correlated with activated partial thromboplastin time (aPTT, r = 0.62 to 0.67). Thrombin activity, measured by FPA, was as closely related to aPTT as to the heparin level. Baseline levels of F1.2 were significantly related to the risk of death or reinfarction at 30 days (p = 0.008); values 12 h after enrollment also were related to 30-day mortality (p = 0.05).
  
  
  CONCLUSIONS
  Although intravenous heparin partly suppresses the increased thrombin activity associated with thrombolysis, it does not inhibit thrombin generation. The aPTT was as good a measure of suppression of thrombin activity as the heparin level itself. Hematologic markers of thrombin generation were found to be related to the subsequent risk of thrombotic events.
authors.affiliation: Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: C B
authors.initials: CB
authors.lastname: Granger
authors.forename: R
authors.initials: R
authors.lastname: Becker
authors.forename: R P
authors.initials: RP
authors.lastname: Tracy
authors.forename: R M
authors.initials: RM
authors.lastname: Califf
authors.forename: E J
authors.initials: EJ
authors.lastname: Topol
authors.forename: K S
authors.initials: KS
authors.lastname: Pieper
authors.forename: A M
authors.initials: AM
authors.lastname: Ross
authors.forename: S
authors.initials: S
authors.lastname: Roth
authors.forename: C
authors.initials: C
authors.lastname: Lambrew
authors.forename: E G
authors.initials: EG
authors.lastname: Bovill
mesh_terms: D000368:Aged; D000990:Antithrombin III / Q000187:drug effects / Q000378:metabolism; D015986:Confounding Factors, Epidemiologic; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D005344:Fibrinopeptide A / Q000187:drug effects / Q000378:metabolism; D006493:Heparin / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy*; D010447:Peptide Hydrolases / Q000187:drug effects / Q000378:metabolism; D013300:Streptokinase / Q000627:therapeutic use*; D013917:Thrombin / Q000187:drug effects* / Q000378:metabolism*; D015912:Thrombolytic Therapy; D013927:Thrombosis / Q000209:etiology / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; C046193:antithrombin III-protease complex; D005344:Fibrinopeptide A; D000990:Antithrombin III; D006493:Heparin; D010447:Peptide Hydrolases; D013300:Streptokinase; D013917:Thrombin