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Usefulness of fibrinogenolytic and procoagulant markers during thrombolytic therapy in predicting clinical outcomes in acute myocardial infarction. TIMI-5 Investigators. Thrombolysis in Myocardial Infarction.

Abstract
Thrombin activity is increased in the setting of acute myocardial infarction (AMI) and has been shown to increase further after the administration of thrombolytic therapy for acute infarction. This increase in thrombin activity may play an important role in the 15% to 25% rate of failure to achieve initial reperfusion and in the 5% to 15% rate of early reocclusion after initially successful thrombolysis. To investigate potential mechanisms of thrombin formation in vivo, to understand better the balance of coagulation and fibrinolysis during treatment with recombinant tissue-type plasminogen activator (rt-PA), and to investigate the role of hemostatic markers as predictors of clinical events, we measured 3 markers of procoagulant activity: fibrinopeptide A (FPA), thrombin-antithrombin III complexes (TAT), and prothrombin fragment 1.2 (F1.2), and a marker of fibrinogenolytic activity (B beta 1-42) in patients enrolled in the Thrombolysis in Myocardial Infarction (TIMI)-5 study. This trial was a randomized, dose-ranging, pilot trial of hirudin versus heparin as adjunctive antithrombotic therapy with rt-PA administered to patients with AMI. Correlation of markers at 1 hour with clinical outcomes revealed that increased FPA and TAT levels were associated with increased mortality and TIMI grades 0, 1, or 2 flow at 90 minutes; increased F1.2 levels were associated with TIMI grade 0 or 1 flow at 90 minutes; and increased levels of all 3 procoagulant markers were associated with hemorrhagic events. Late (12 to 24 hours) increases in F1.2, TAT, and B beta 1-42 may be predictive of recurrent ischemia. These results suggest that selected markers of procoagulant and fibrinogenolytic activity may be useful in predicting clinical outcomes in patients treated with thrombolytic therapy for AMI.
AuthorsJ S Scharfstein, D R Abendschein, P R Eisenberg, D George, C P Cannon, R C Becker, B Sobel, L A Cupples, E Braunwald, J Loscalzo
JournalThe American journal of cardiology (Am J Cardiol) Vol. 78 Issue 5 Pg. 503-10 (Sep 01 1996) ISSN: 0002-9149 [Print] United States
PMID8806332 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial)
Chemical References
  • Biomarkers
  • Fibrin Fibrinogen Degradation Products
  • Fibrinolytic Agents
  • Peptide Fragments
  • Recombinant Proteins
  • antithrombin III-protease complex
  • fibrinogen Bbeta (15-42)
  • prothrombin fragment 1.2
  • Fibrinopeptide A
  • Antithrombin III
  • Prothrombin
  • Heparin
  • Peptide Hydrolases
Topics
  • Antithrombin III (analysis)
  • Biomarkers
  • Fibrin Fibrinogen Degradation Products (analysis)
  • Fibrinolytic Agents (therapeutic use)
  • Fibrinopeptide A (analysis)
  • Hemostasis
  • Heparin (therapeutic use)
  • Hirudin Therapy
  • Humans
  • Myocardial Infarction (drug therapy)
  • Peptide Fragments (analysis)
  • Peptide Hydrolases (analysis)
  • Pilot Projects
  • Prothrombin (analysis)
  • Recombinant Proteins
  • Thrombolytic Therapy
  • Treatment Outcome

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