Tissue factor pathway inhibitor - cofactor-dependent regulation of the initiation of coagulation.

PURPOSE OF REVIEW

In humans, tissue factor pathway inhibitor (TFPI) exists in two alternatively spliced isoforms, TFPIα and TFPIβ. TFPIα consists of three Kunitz domains (K1, K2 and K3) and a highly basic C-terminal tail. K1 inhibits the tissue factor-activated factor VII complex, K2 specifically inhibits activated factor X, K3 is essential for interaction with its cofactor, protein S, and the basic C-terminus is binds factor V-short (FV-short) with high affinity. TFPIβ consists of K1 and K2 that is glycosylphosphatidylinositol anchored directly to cell surfaces. This review explores the structure/function of TFPI and its cofactors (protein S and FV-short), and the relative contributions that different TFPI isoforms may play in haemostatic control.

RECENT FINDINGS

Recent data have underscored the importance of TFPIα function and its reliance on its cofactors, protein S and FV-short, in influencing haemostatic control as well as bleeding and thrombotic risk.

SUMMARY

TFPIα is likely the most important pool of TFPI in modifying the risk of thrombosis and bleeding. TFPIα forms a trimolecular complex with FV-short and protein S in plasma. FV-short expression levels control the circulating levels of TFPIα, whereas protein S exerts essential cofactor mediated augmentation of it anticoagulant function.