Skip to main content
SpringerLink
Log in
Book cover

Nonanticoagulant Actions of Glycosaminoglycans pp 227–233Cite as

TFPI Release by GAGs and Its Role in Their Mechanism of Action

  • Chapter

  • 40 Accesses

Abstract

Tissue factor pathway inhibitor (TFPI) formerly named Extrinsic Pathway Inhibitor (EPI) or Lipoprotein Associated Coagulation Inhibitor (LACI) is a Kunitz-type protein with three inhibitory domains1. The first domain binds to the tissue factor/factor VII a — complex, while the second one has been identified as the factor Xa binding site. The third domain is probably involved in the association of TFPI with plasma lipoproteins and heparins1,2. TFPI inhibitory activity as well as antigen level in plasma can be measured but there are large discrepances between TFPI results from the functional and immunologic assays. It has been recently postulated that only the free form of TFPI is biologically active3. TFPI is synthesized in endothelial cells and megakariocytes4,5. In normal individuals there is a quite broad range of TFPI activities and antigen levels ranging from 50 to 170 ng/ml6,7,8. The biggest TFPI-pool is bound to the main site of its synthesis -endothelium. About 90% of blood TFPI is associated with lipoproteins9,10. The major part with LDL, less with HDL. About 5% plasma TFPI remains in a free form. TFPI has also been found in platelets — about 8% of the whole blood TFPI5 (Fig.1). Tissue factor pathway inhibitor has a double, two step inhibitory effect. It inhibits the active factor X and in a complex with this factor TFPI binds to the tissue factor/factor VIIa complex inhibiting its enzymatic activity11,12 (Fig.2).

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Wun TC, Kretzmer KK, Girard TJ, Mieletich JP, Broze GJ Jr: Cloning and characterisation of a cDNA coding for the lipoprotein-associated coagulation inhibitor shows that it consists of three tandem Kunitz-type inhibitory domains. J Biol Chem 1988;263:6001–6004.

    PubMed  CAS  Google Scholar 

  2. Enjyoji K, Miyata T, Kato H, Kamikubo Y. Identification of Kunitz domain 3 of tissue factor pathway inhibitor (TFPI) as second heparin binding site for the optimal inhibition of factor Xa. Thromb Haemstas 1993;69:680.

    Google Scholar 

  3. Radziwon P, Boczkowska-Radziwon B, Schenk J, Fareed J, Breddin HK: Eine neue Methode zur Bestimmung des freien TFPI im Plasma. Vasa 1994;Supp 43:17.

    Google Scholar 

  4. Bajaj MS, Kuppuswamy MN, Saito H, Spitzer SG, Bajaj SP: Cultured normal human hepatocytes do not synthesize lipoprotein-associated coagulation inhibitor: Evidence that endothelium is the principal site of its synthesis. Proc Natl Acad Sci USA 1990;87:8869–8873.

    Article  PubMed  CAS  Google Scholar 

  5. Novotny WF, Girard TJ, Miletich JP, Broze GJ Jr: Platelets secrete a coagulation inhibitor functionally and antigenically similar to the lipoprotein associated coagulation inhibitor. Blood 1988;72:2020–2025.

    PubMed  CAS  Google Scholar 

  6. Novotny WF, Brown SG, Miletich JP, Rader DJ, Broze JJr: Plasma antigen levels of the lipoprotein-associated coagulation inhibitor in patients samples. Blood 1991;78:387–393.

    PubMed  CAS  Google Scholar 

  7. Warr TA, Warn-Cramer BJ, Rao LVM, Rapaport SI: Human plasma extrinsic pathway inhibitor activity: I: Standarization of assay and evaluation of physiological variables. Blood 1989;74:201–206.

    PubMed  CAS  Google Scholar 

  8. Sandset PM, Larsen ML, Abildgaard U: Chromogenic substrate assay of extrinsic pathway inhibitor (EPI): levels in the normal population and relation to cholesterol. Blood Coagul Fibrinol 1991;2:425–433.

    Article  CAS  Google Scholar 

  9. Hubbard AR, Jennings CA: Inhibition of the tissue factor-factor VII complex: Involvement of factor Xa and lipoproteins. Thromb Res 1987;46:527–537.

    Article  PubMed  CAS  Google Scholar 

  10. Novotny WF, Girard TJ, Mieletich JP, Broze GJ Jr: Purification and characterisation of the lipoprotein-associated coagulation inhibitor from human plasma. J.Biol.Chem. 1989; 264:18832–18837.

    PubMed  CAS  Google Scholar 

  11. Broze GJ Jr, Warren LA, Novotny WF, Higuchi DA, Girard TJ, Mieletich JP: The lipoprotein-associated coagulation inhibitor that inhibits the factor VII-tissue factor complex also inhibits factor Xa: Insight into its possible mechanism of action. Blood 1988;71:335–343.

    PubMed  CAS  Google Scholar 

  12. Broze GJ Jr, Girard TJ, Novotny WF: Regulation of coagulation by a multivalent Kunitz-type inhibitor. Biochemistry 1990;29:7539–7546.

    Article  PubMed  CAS  Google Scholar 

  13. Rosenberg RD: Chemistry of the hemostatic mechanism and its relationship to the action of heparin. Fed Proc 1977;36:10–14.

    PubMed  CAS  Google Scholar 

  14. Holmer E, Kurachi K, Soderstrom G: The molecular weight dependence of the rate-enhancing effect of heparin on the inhibition of thrombin, factor Xa, factor IXa, factor XIa, factor XIIa, and kallikrein by antithrombin III. Biochem J 1981;193:395–401.

    PubMed  CAS  Google Scholar 

  15. Casu B: Structure and biological activity of heparin. Adv Carbohydr Chem Biochem 1985;43:51–54.

    Article  PubMed  CAS  Google Scholar 

  16. Tollefsen DM, Blank MK: Detection of a new heparin-dependent inhibitor of thrombin in human plasma. J Clin Invest 1981;68:589–596.

    Article  PubMed  CAS  Google Scholar 

  17. Bendetowicz AV, Pacaud E, Bequin S, Uzan A, Hemker HC: On the relationship between molecular mass and anticoagulant activity of a low molecular weight heparin (enoxaparin). Thromb Haemostas 1992;67:556–562.

    CAS  Google Scholar 

  18. Sandset PM, Abilgarard U, Larsen ML: Heparin induces release of extrinsic coagulation pathway inhibitor (EPI). Thromb Res 1988;50:803–813.

    Article  PubMed  CAS  Google Scholar 

  19. Harenberg J, Acker M, Jeschek M: Proposed binding sequence of tissue factor pathway inhibitor with heparins. Thromb Haemostas 1993;69:681.

    Google Scholar 

  20. Valentin S, Østergaard P, Nilsen JI, Nordfang O: Comparison of different glycosaminoglycans with respect to their capacity for binding of tissue factor pathway inhibitor. Thromb Haemostas 1993;69:682.

    Google Scholar 

  21. Wun T. Lipoprotein-associated coagulation inhibitor (LACI) is a cofactor for heparin: Synergistic anticoagulant action between LACI and sulfated polysaccharides. Blood 1992;79:430–438.

    CAS  Google Scholar 

  22. Harenberg J, Siegle M, Dempfe CE, Stehle G, Heene D: Protamine neutralization of the release of tissue factor pathway inhibitor activity by heparins. Thromb Haemostas 1993;70:942–945.

    CAS  Google Scholar 

  23. Hoist J, Lindbald B, Bergovist D, Hedner U, Garre K, Nordfang O, Østergaard P: Effect of protamine sulfate on tissue factor pathway inhibitor (TFPI) released by iv or sc standard or low molecular weight heparin. Thromb Haemostas 1993;69:1114.

    Google Scholar 

  24. Radziwon P, Weichert W, Boczkowska-Radziwon B, Schenk J, Hoppenstaedt D, Fareed J, Breddin HK: Effects of TFPI on blood coagulation in vitro and on laser induced thrombus formation in rat mesenterium. Annals of Hematology 1994; 68(Supp.II): A106.

    Google Scholar 

  25. Boczkowska-Radziwon B, Radziwon P, Schenk J, Butti A, Breddin HK: Die antikoagulatorische Wirkung von supersulfatiertem, niedermolekularem Heparin (SSH) ist durch TFPI-Freisetzung vermittelt. In Endothelfunktion und Arteriosklerose. Heinle H, Schulte H, Breddin HK eds. 1994:184–188.

    Google Scholar 

  26. Day KC, Hoffman LC, Palmier MO, Kretzmer KK, Huang MD, Pyla EY, Spokas E, Broze GJJr, Warren TG, Wun TC: Recombinant lipoprotein-associated coagulation inhibitor inhibits tissue thromboplastin-induced intravascular coagulation in the rabbit. Blood 1990;76:1538–1545.

    PubMed  CAS  Google Scholar 

  27. Creasey AA, Chang ACK, Feigen L, Wun TC, Taylor FBJr, Hinshaw LB: Tissue factor pathway inhibitor reduces mortality from Escherichia coli septic shock. J Clin Invest 1993;91:2850–2860.

    Article  PubMed  CAS  Google Scholar 

  28. Haskel EJ, Torr SR, Day KC, Palmier MO, Wun TC, Sobel BE, Abendschein DR: Prevention of arterial reocclusion after thrombolysis with recombinant lipoprotein-associated coagulation inhibitor. Circulation 1991;84:821–827.

    PubMed  CAS  Google Scholar 

  29. Spokas EG, Wun TC: Venous thrombosis produced in the vena cava of rabbits by vascular damage and stasis. JPM 1992;27:225–232.

    CAS  Google Scholar 

  30. Khouri RK, Kondsi B, Kaiding Ornberg RL, Wun TC: prevention of thrombosis by topical application of tissue factor pathway inhibitor in a rabbit model of vascular trauma. Ann Plast Surg 1993;30:398–404.

    Article  PubMed  CAS  Google Scholar 

  31. Nordfang O, Bjorn SE, Valentin S, Nielsen LS, Wildgoose P, Beck TC, Hedner U: The C-terminal of tissue factor pathway inhibitor is essential to its anticoagulant activity. Biochemistry 1991;30:10371–10376.

    Article  PubMed  CAS  Google Scholar 

  32. Holst J, Lindbald B, Bergqvist D, Nordfang O, Østergaard PB, Petersen JGL, Nielsen G, Hedner U: Antithrombotic effect of recombinant truncated tissue factor pathway inhibitor (TFPI1–161) in experimental venous thrombosis — a comparison with low molecular weight heparin. Thromb Haemostas 1994;71:214–219.

    CAS  Google Scholar 

  33. Bregengard Nordfang O, Wildgoose P, Diness V, Hedner U: Effect of two-domain TFPI on endotoxin-in-duced disseminated intravascular coagulation in rabbits. Thromb Haemostas 1993;69:887.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dept. of Angiology, Center of Internal Medicine, J.W.Goethe University, Frankfurt am Main, Germany

    J. Schenk, B. Boczkowska-Radziwon & Hans K. Breddin

  2. Dept. of Haematology, University Medical School, Bialystok, Poland

    Piotr Radziwon

  3. Regional Blood Transfusion Center, Bialystok, Poland

    Piotr Radziwon

  4. Hemostasis Research Laboratories, Loyola University Medical Center, Maywood, Illinois, USA

    Jawed Fareed

Authors
  1. Piotr Radziwon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Schenk
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B. Boczkowska-Radziwon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jawed Fareed
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hans K. Breddin
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of Heidelberg, Mannheim, Germany

    Job Harenberg

  2. G. Ronzoni Institute, Milan, Italy

    Benito Casu

Rights and permissions

Reprints and permissions

Copyright information

© 1996 Plenum Press, New York

About this chapter

Cite this chapter

Radziwon, P., Schenk, J., Boczkowska-Radziwon, B., Fareed, J., Breddin, H.K. (1996). TFPI Release by GAGs and Its Role in Their Mechanism of Action. In: Harenberg, J., Casu, B. (eds) Nonanticoagulant Actions of Glycosaminoglycans. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-0371-8_17

Download citation

  • DOI: https://doi.org/10.1007/978-1-4613-0371-8_17

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-8021-4

  • Online ISBN: 978-1-4613-0371-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation