Factors VII, X, Tissue Factor, and the Tissue Repair Mechanism

The great discoveries of science often consist in the uncovering of a truth buried under the rubble of traditional prejudice, in getting out of the cul-de-sacs into which formal reasoning divorced from reality leads; in liberating the mind trapped between the iron teeth of dogma. --Arthur Koestler "The Sleepwalkers: A History of Man's Changing Vision of the Universe" page 214 


 

 

The interaction of factor VII with tissue factor and factor X is the engine of embryological development, tissue maintenance, and tissue repair. It is the essence of the tissue repair mechanism, which is a sub-component of the mammalian stress mechanism.

Like factor VIIIC, factor VII is so labile that its enzymatic activity is negligible unless it is stabilized by tissue factor, which is a glycoprotein that is produced by extravascular cells. Factor VII is secreted into flowing blood by the liver and isolated from tissue factor by the vascular endothelium. Damage to the vascular endothelium directly exposes factor VII to tissue factor, which triggers the interaction of factors VII, VIII, IX and X that accelerates insoluble fibrin generation to enable clot formation. The gigantic size of factor VIII prevents it from penetrating the clot of its own manufacture, which limits clot formation to the immediate vicinity of tissue damage. The viscoelastic clot governs the passage of factors VII and X into the damaged tissues, where they interact with tissue factor. The complex of factor VII and tissue factor generates small amounts of thrombin and interacts with factor X, which amplifies thrombin generation to energize embryological development and tissue repair. 

Normally the selectively permeable clot maintains thrombin generation within a narrow range to optimize tissue repair, but combinations of severe, unremitting environmental stress can induce hyperactivity of this engine of tissue repair, causing cancer, which is a self-sustaining state of tissue repair hyperactivity that continuously invades adjacent healthy tissues, exposes tissue factor, and stimulates harmful nociception that sustains the vicious cycle of malignancy. 

Defects in factor VII, tissue factor, or factor X are seldom survivable because they disrupt embryological development. Warfarin, thalidomide, and other pharmaceuticals that disrupt their interaction are potentially lethal because they disrupt embryological development, tissue maintenance, and tissue repair. However, such drugs also inhibit malignancy. 

In contrast, defects in factors VIII, IX, and XIII affect only coagulation, so that pharmaceuticals such as heparin that inhibit their activity do not disrupt embryological development, tissue maintenance, tissue repair, or malignancy.