Tissue Factor Pathway Inhibitor [Tfpi]: A Natural Coagulation Inhibitor and Potential Therapeutic Agent – A Review

Abstract

Abstract It is now well established that the prime trigger to blood coagulation in vivo is tissue factor (TF) that is exposed on the surface of fibroblasts as a result of vessel wall injury. TF joins activated factor VII (FVIIa) normally present in the circulating blood and the TF-FVIIa complex converts FX to FXa. TF activity and the extrinsic pathway of blood coagulation in general are regulated by the specific and major physiological circulating inhibitor: “ tissue factor pathway inhibitor -TFPI”. TFPI binds to factor Xa and, in this combination, binds to and inhibits tissue factor/factor VIIa complex and activated FX (FXa) and thus TFPI is currently being included as a natural coagulation inhibitor. TFPI is synthesized primarily by the vascular endothelium. TFPI is distributed in three pools in vivo ; about 80 to 85% of the total body TFPI is associated with endothelial cell-surface, presumably involving glycosaminoglycans and proteoglycans and 15-20% is blood-born circulating in plasma, of which 80% bound to lipoproteins and the rest is the free form, and a tiny proportion (∼3%) is found in platelets. The TFPI that is free in plasma is the physiologically active anticoagulant part of TFPI. The importance of TFPI as a natural coagulation inhibitor is reflected by the role TFPI plays in several diseases, as detected by its plasma levels, presence of TF and TFPI in pathologic specimens as well as the effect of exogenously administered recombinant TFPI (rTFPI) on thrombosis, in both humans and animal models. Recent literature is reviewed on the involvement of TFPI in diseases like: Atherosclerosis, arterial thrombosis, Restenosis following arterial intervention, Stroke and ischemia reperfusion injury, Deep Venous Thrombosis (DVT) and anti-phospholipid antibody syndrome, Acute Lung Injury, Malignancy particularly the metastasis of tumor cell, Chronic renal failure (CRF), nephrotic syndrome, crescentic glomerulonephritis, and thrombosis associated with paroxysmal nocturnal hemoglobinuria (PNH). Lastly, a short account is added on the potential Therapeutic Uses of TFPI. Conclusion This review article aims to highlight the importance of yet another natural coagulation inhibitor (TFPI), like earlier inhibitors, its deficiency in numerous disease conditions led to the elaboration of recombinant TFPI (rTFPI) which holds much promise in the future therapy of thrombotic disease.