Tissue factor

Abstract

The transmembrane glycoprotein tissue factor (TF) is the initiator of the coagulation cascade in vivo. When TF is exposed to blood, it forms a high-affinity complex with the coagulation factors factor VII/activated factor VIIa (FVII/VIIa), activating factor IX and factor X, and ultimately leading to the formation of an insoluble fibrin clot. TF plays an essential role in hemostasis by restraining hemorrhage after vessel wall injury. An overview of biological and physiological aspects of TF, covering aspects consequential for thrombosis and hemostasis such as TF cell biology and biochemistry, blood-borne (circulating) TF, TF associated with microparticles, TF encryption-decryption, and regulation of TF activity and expression is presented. However, the emerging role of TF in the pathogenesis of diseases such as sepsis, atherosclerosis, certain cancers and diseases characterized by pathological fibrin deposition such as disseminated intravascular coagulation and thrombosis, has directed attention to the development of novel inhibitors of tissue factor for use as antithrombotic drugs. The main advantage of inhibitors of the TF*FVIIa pathway is that such inhibitors have the potential of inhibiting the coagulation cascade at its earliest stage. Thus, such therapeutics exert minimal disturbance of systemic hemostasis since they act locally at the site of vascular injury.

A Study of the Expression of Functional Human Coagulation Factor IX in Keratinocytes Using a Nonviral Vector Regulated by K14 Promoter

“…Therefore, the use of human pool plasma for drawing the standard curve in addition to the application of polyclonal anti-hFIX to perform ELISA could underestimate the antigenicity of the hFIX presents in the samples taken from serumfree media. The relatively higher levels of rhFIX, estimated from the clotting tests, could also be correlated to a probable occurrence of an extrinsic coagulation, which might be mediated by a tissue factor released from the cultured keratinocytes, as suggested by others [45]. However, since basal coagulation activity was not detected in either of the negative controls, thus, the possibility of basal coagulation activity in the serum-free media used in this work is ruled out.…”

The role of blood cells and their microparticles in blood coagulation

“…Activated platelets are also exposing partially activated FV, which may be important before traces of thrombin have formed to activate plasma FV, since platelet-derived FVa appeared to be essential in FXa activation of FVIIa [3]. For further details of this proposed model of coagulation, we refer to recent review articles on this topic [4,5].…”

“…In addition, TF can be up-regulated on circulating monocytes (for a review, see [4]). An early assessment of the gross distribution of TF was accomplished by testing different tissues for overall TF activity.…”

“…Such an activation is accompanied by surface expression of TF. Lymphokines and pro-inflammatory cytokines also induce monocyte TF expression [4]. TF expression by cells of the monocyte lineage is accompanied by activation of inflammatory and immune responses.…”

Activated Monocytes Enhance Platelet-Driven Contraction of Blood Clots via Tissue Factor Expression

“…In particular, inflammatory cells such as monocytes are known to express tissue factor (TF) on their surfaces in various disease states such as atherosclerosis, heart disease, and severe sepsis 10–12 . TF expression is known to occur following activation with agonists such as phorbol-12-myristate-13-acetate (PMA) and bacterial lipopolysaccharide 13, 14 .…”