The multivalent activity of the tissue factor-thrombin pathway in thrombotic and non-thrombotic disorders as a target for therapeutic intervention

Expert Opin Ther Targets. 2011 Jan;15(1):75-89. doi: 10.1517/14728222.2011.532788. Epub 2010 Nov 10.


Importance of the field: Tissue factor (TF) is the key initiator of the coagulation cascade. The exposure of subendothelial TF after vessel injury to blood is a critical step in hemostasis and in the pathogenesis of arterial and venous thrombotic disorders. Moreover, an additional role for TF overexpression and subsequent generation of TF:FVIIa complex, FXa and thrombin have been recently emerged, contributing in non-thrombotic manifestations such as inflammation, cancer growth and fibrosis.

Areas covered in this review: The multivalent role of TF and the above mentioned proteases in disease is reviewed, with focus on their implication in non-thrombotic disorders, as suggested by clinical and experimental data. Moreover, potential therapeutic interventions using anticoagulation agents are discussed.

What the reader will gain: A better understanding of the pathogenic role of the TF-thrombin pathway in the pathogenesis of disease and the effect of anticoagulants in the treatment of such disorders.

Take home message: The TF-thrombin pathway, apart from the initiation of hemostasis and thrombosis, exert intracellular signaling activity through protease-activated receptors, participating in inflammation and tumor biology. Both low-molecular-weight heparins and recently developed anticoagulants rise as candidates for the modification of biological functions associated with disorders like sepsis, ischemia-reperfusion or cancer growth and metastasis.

Publication types

  • Review

MeSH terms

  • Animals
  • Anticoagulants / pharmacology
  • Blood Coagulation / physiology
  • Drug Delivery Systems*
  • Hemostasis
  • Heparin, Low-Molecular-Weight / pharmacology
  • Humans
  • Thrombin / metabolism*
  • Thromboplastin / metabolism*
  • Thrombosis / drug therapy
  • Thrombosis / physiopathology


  • Anticoagulants
  • Heparin, Low-Molecular-Weight
  • Thromboplastin
  • Thrombin