Effect of intravenous heparin infusion on thrombin-antithrombin complex and fibrinopeptide A in unstable angina

Am Heart J. 1998 Dec;136(6):1106-13. doi: 10.1016/s0002-8703(98)70170-x.

Abstract

Background: In unstable angina, the clinical efficacy of heparin is limited in time, and recurrence of adverse events has been reported after discontinuation of the anticoagulant.

Methods: In 21 episodes of unstable angina, we used the plasma level of fibrinopeptide A (FPA) and of thrombin-antithrombin complex (TAT) to evaluate the pattern of thrombin inhibition by heparin and the effect of stopping heparin and initiating aspirin.

Results: At admission, the plasma level of FPA was increased: median value 3.7 ng/mL compared with 5.5 ng/mL in a control group of 20 patients with early myocardial infarction (not significant). The following findings were observed during a 4-day course of intravenous heparin infusion: (1) FPA decreased significantly 6 hours after the start of therapy; (2) FPA was lower when activated partial thromboplastic time (aPTT) was >1.5 times baseline; (3) there was a significant negative correlation between aPTT and FPA. Twenty-four hours after heparin was discontinued and aspirin initiated, a significant increase in TAT and FPA in plasma was observed.

Conclusions: The results confirm ongoing fibrin formation in the active phase of unstable angina, indicate incomplete and variable inhibition of thrombin by heparin during continuous infusion, and suggest a risk of re-emergence of thrombosis (in spite of initiating aspirin) 24 hours after withdrawal of heparin. Data demonstrate a better control of thrombin activity when heparin is infused at rates that maintain aPTT at >1.5 times baseline, as currently recommended in unstable angina.

MeSH terms

  • Aged
  • Angina, Unstable / blood*
  • Angina, Unstable / drug therapy*
  • Anticoagulants / administration & dosage*
  • Anticoagulants / therapeutic use
  • Antithrombin III / analysis*
  • Aspirin / administration & dosage
  • Aspirin / therapeutic use
  • Biomarkers / blood
  • Female
  • Fibrinopeptide A / analysis*
  • Heparin / administration & dosage*
  • Heparin / therapeutic use
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Peptide Hydrolases / analysis*
  • Prospective Studies

Substances

  • Anticoagulants
  • Biomarkers
  • antithrombin III-protease complex
  • Fibrinopeptide A
  • Antithrombin III
  • Heparin
  • Peptide Hydrolases
  • Aspirin