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


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.
Ott
Ilka
I
Medizinische Klinik und Deutsches Herzzentrum der Technischen Universität München, Germany. ott@dhm.mhn.de
Malcouvier
Valerie
V
Schömig
Albert
A
Neumann
Franz-Josef
FJ
D000077284:Abciximab; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002460:Cell Line; D002478:Cells, Cultured; D017023:Coronary Angiography; D004562:Electrocardiography; D005260:Female; D005341:Fibrinolysin / Q000494:pharmacology; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use; D007700:Kinetics; D008074:Lipoproteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D009203:Myocardial Infarction / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism* / Q000628:therapy; D015607:Stents; D015912:Thrombolytic Therapy; D013925:Thromboplastin / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D005343:Fibrinolytic Agents; D007140:Immunoglobulin Fab Fragments; D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor; D013925:Thromboplastin; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D000077284:Abciximab