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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Democritus University of Thrace, Department of Internal Medicine, Alexandroupolis, Greece.
Ioannis
I
Mitroulis
Konstantinos
K
Kambas
Panagiota
P
Anyfanti
Michael
M
Doumas
Konstantinos
K
Ritis
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D001777:Blood Coagulation / Q000502:physiology; D016503:Drug Delivery Systems; D006487:Hemostasis; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology; D006801:Humans; D013917:Thrombin / Q000378:metabolism*; D013925:Thromboplastin / Q000378:metabolism*; D013927:Thrombosis / Q000188:drug therapy / Q000503:physiopathology
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D013925:Thromboplastin; D013917:Thrombin