Thromb Haemost 2005; 93(01): 35-39
DOI: 10.1160/TH04-06-0393
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Tissue factor pathway inhibitor on circulating microparticles in acute myocardial infarction

Birgit Steppich
1   Deutsches Herzzentrum und 1. Medizinische Klinik der Technischen Universität München, Germany
,
Christoph Mattisek
1   Deutsches Herzzentrum und 1. Medizinische Klinik der Technischen Universität München, Germany
,
Dean Sobczyk
1   Deutsches Herzzentrum und 1. Medizinische Klinik der Technischen Universität München, Germany
,
Adnan Kastrati
1   Deutsches Herzzentrum und 1. Medizinische Klinik der Technischen Universität München, Germany
,
Albert Schömig
1   Deutsches Herzzentrum und 1. Medizinische Klinik der Technischen Universität München, Germany
,
Ilka Ott
1   Deutsches Herzzentrum und 1. Medizinische Klinik der Technischen Universität München, Germany
› Author Affiliations
Financial support: Supported in part by grants from the Deutsche Forschungsgemeinschaft (Ot 158/4–1), the Bayerische Wissenschaftsministerium (Habilitationsförderpreis I.O.) and the Gesellschaft für Thrombose und Hämostase.
Further Information

Publication History

Received 24 June 2004

Accepted after resubmission 25 October 2004

Publication Date:
14 December 2017 (online)

Summary

In acute myocardial infarction (AMI), increased Tissue Factor (TF) expression on circulating monocytes and microparticles (MP) may contribute to thrombotic events. Because surfaceboundTissue Factor Pathway Inhibitor-1 (TFPI) inhibitsTF activity on monocytes and endothelial cells decreased TFPI expression may reinforce the procoagulant activity of circulating MP.Aim of the study was to analyze TFPI expression and TF activity after stenting and thrombolysis inAMI.Thirty-nine patients of a randomized study comparing intravenous thrombolysis (n = 19) and stenting (n = 20) were included. Before and after therapy blood samples for analysis of MPs, TF antigen and activity, prothrombin fragment F1+2 and D-dimer were obtained.TFPI expression on TF positive MPs was decreased after thrombolysis but not after stenting. In contrast, TF plasma levels and TF positive MP remained unchanged in both treatment groups. After thrombolysis increased D-dimer and F1+2 plasma concentrations indicated activation of fibrinolysis and coagulation. Significance of MPTFPI for inhibition ofTF activity was measured using inhibitory TFPI antibodies. Membrane-associated TFPI inhibited TF activity on circulating MPs. After thrombolysis inhibition of TF activity by TFPI was decreased as compared to stenting. Correlation of circulating TF with F1+2 only after thrombolysis, suggests a role forTF-induced activation of coagulation after thrombolysis. Enhanced TF activity on circulating MPs inAMI is inhibited by endogenous surface-boundTFPI.After thrombolysis but not after stenting MPTFPI is degraded and may induce thrombin generation due to unopposed tissue factor activity. Anti-TF therapies during thrombolysis may reduce thrombin generation in AMI.

 
  • References

  • 1 Keeley E, Boura J, Grines C. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet 2003; 361: 13-20.
  • 2 Ott I. et al Reversible regulation of tissue factor-induced coagulation by glycosyl phosphatidylinositolanchored tissue factor pathway inhibitor. Arterioscler Thromb Vasc Biol 2000; 20: 874-82.
  • 3 Ott I. et al Proteolysis of tissue factor pathway inhibitor- 1 by thrombolysis in acute myocardial infarction. Circulation 2002; 105: 279-81.
  • 4 Ott I, Andrassy M, Zieglgansberger D. et al Regulation of monocyte procoagulant activity in acute myocardial infarction: role of tissue factor and tissue factor pathway inhibitor-1. Blood 2001; 97: 3721-6.
  • 5 Soejima H, Ogawa H, Yasue H. et al Heightened tissue factor associated with tissue factor pathway inhibitor and prognosis in patients with unstable angina. Circulation 1999; 99: 2908-13.
  • 6 Giesen PL, Rauch U, Bohrmann B. et al Bloodborne tissue factor: another view of thrombosis. Proc Natl Acad Sci U S A. 1999; 96: 2311-5.
  • 7 Bogdanov V. et al Alternatively spliced human tissue factor: a circulating, soluble, thrombogenic protein. Nat Med 2003; 9: 458-62.
  • 8 Mallat Z. et al Elevated levels of shed membrane microparticles with procoagulant potential in the peripheral circulating blood of patients with acute coronary syndromes. Circulation 2000; 101: 841-3.
  • 9 Schomig A. et al Coronary stenting plus platelet glycoprotein IIb/IIIa blockade compared with tissue plasminogen activator in acute myocardial infarction. Stent versus thrombolysis for occluded coronary arteries in patients with acute myocardial infarction study investigators. N Engl J Med. 2000; 343: 385-91.
  • 10 Combes V, Simon A, Grau G. et al In vitro generation of endothelial microparticles and possible prothrombotic activity in patients with lupus anticoagulant. J Clin Invest 1999; 104: 93-102.
  • 11 Kato H. Regulation of functions of vascular wall cells by tissue factor pathway inhibitor: basic and clinical aspects. Arterioscler Thromb Vasc Biol 2002; 22: 539-48.
  • 12 Nieuwland R. et al Cellular origin and procoagulant properties of microparticles in meningococcal sepsis. Blood 2000; 95: 930-5.
  • 13 Li A, Wun TC. Proteolysis of tissue factor pathway inhibitor (TFPI) by plasmin: effect on TFPI activity. Thromb Haemost 1998; 80: 423-7.
  • 14 Higuchi DA, Wun TC, Likert KM. et al The effect of leukocyte elastase on tissue factor pathway inhibitor. Blood 1992; 79: 1712-9.
  • 15 Belaaouaj A, Li A, Wun T. et al Matrix metalloproteinases cleave tissue factor pathway inhibitor: effects on coagulation. J Biol Chem 2000; 275 (35) 27123-8.
  • 16 Ott I. et al Procoagulant inflammatory responses of monocytes after direct balloon angioplasty in acute myocardial infarction. Am J Cardiol 1998; 82: 938-42.
  • 17 Rauch U, Nemerson Y. Circulating tissue factor and thrombosis. Curr Opin Hematol 2000; 7: 273-7.
  • 18 Falati S, Liu Q, Gross P. et al Accumulation of tissue factor into developing thrombi in vivo is dependent upon microparticle P-selectin glycoprotein ligand 1 and platelet P-selectin. J Exp Med 2003; 197: 1585-98.
  • 19 Fassbender K, Dempfle CE, Mielke O. et al Changes in coagulation and fibrinolysis markers in acute ischemic stroke treated with recombinant tissue plasminogen activator. Stroke 1999; 30: 2101-4.
  • 20 Steiner S, Ahmadi R, Willfort A. et al Hemostatic markers with bolus versus prolonged heparin after carotid artery stenting. Thromb Res 2003; 109: 23-9.
  • 21 Lupu C. et al Cellular effects of heparin on the production and release of tissue factor pathway inhibitor in human endothelial cells in culture. Arterioscler Thromb Vasc Biol 1999; 19: 2251-62.
  • 22 Stalboerger PG. et al Plasmin proteolysis of endothelial cell and vessel wall associated tissue factor pathway inhibitor. Thromb Haemost 2001; 86: 923-8.
  • 23 Li Y, Spencer FA, Becker RCJ. Plasmin-mediated proteolysis of vascular endothelial cell heparin releasable tissue factor pathway inhibitor. Thromb Thrombolysis 2003; 15: 19-23.
  • 24 Leon C, Alex M, Klocke A. et al Platelet ADP receptors contribute to the initiation of intravascular coagulation. Blood 2004; 103: 594-600.