Proteolysis of tissue factor pathway inhibitor-1 by thrombolysis in acute myocardial infarction

Circulation. 2002 Jan 22;105(3):279-81. doi: 10.1161/hc0302.103591.


Background: In acute myocardial infarction (AMI), surface-bound tissue factor pathway inhibitor-1 (TFPI-1) inhibits an increased monocyte procoagulant activity. In addition, TFPI-1 is released from microvascular endothelial cells after treatment with heparin and thereby contributes to its antithrombotic properties.

Methods and results: We examined 19 patients in a randomized study comparing intravenous fibrinolysis with alteplase (n=9) and revascularization by stent placement with additional abciximab treatment (n=10). We obtained blood samples for analysis of monocytic TFPI-1 surface expression by flow cytometry and plasma TFPI-1 concentrations by immunoassay before and after therapy. We found a significant decrease in surface TFPI-1 on circulating monocytes 24 hours after thrombolysis (P=0.006) that was not observed after stenting. Systemic plasma TFPI-1 concentrations increased immediately after stenting by 71+/-14% (P=0.008), whereas after thrombolysis, a decrease in TFPI-1 plasma concentrations of 21+/-11% was observed (P=0.075). In vitro experiments confirmed that plasmin decreased TFPI-1 surface expression dose-dependently.

Conclusions: Activation of the fibrinolytic system by alteplase in AMI decreases surface-associated TFPI-1 on circulating monocytes and plasma TFPI-1. Reduced TFPI-1 may contribute to thrombotic complications after fibrinolysis in AMI.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abciximab
  • Adult
  • Aged
  • Antibodies, Monoclonal / therapeutic use
  • Cell Line
  • Cells, Cultured
  • Coronary Angiography
  • Electrocardiography
  • Female
  • Fibrinolysin / pharmacology
  • Fibrinolytic Agents / therapeutic use*
  • Humans
  • Immunoglobulin Fab Fragments / therapeutic use
  • Kinetics
  • Lipoproteins / metabolism*
  • Male
  • Middle Aged
  • Monocytes / metabolism
  • Myocardial Infarction / diagnosis
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / metabolism*
  • Myocardial Infarction / therapy
  • Stents
  • Thrombolytic Therapy*
  • Thromboplastin / metabolism
  • Tissue Plasminogen Activator / therapeutic use*


  • Antibodies, Monoclonal
  • Fibrinolytic Agents
  • Immunoglobulin Fab Fragments
  • Lipoproteins
  • lipoprotein-associated coagulation inhibitor
  • Thromboplastin
  • Tissue Plasminogen Activator
  • Fibrinolysin
  • Abciximab