About TFPI / Tissue Factor Pathway Inhibitor:
Tissue factor pathway inhibitor, also known as TFPI, is a single-chain polypeptide that can inhibit Factor Xa, which allows the Xa-TFPI complex to inhibit the FVIIa-tissue factor complex. It’s located on chromosome 2q31-q32.1 and has nine exons which span 70 kb. TFPI is present in human plasma in three forms: as an LDL/VLDL-associated form, an HDL-associated form and a free form.
As a protease inhibitor with three Kunitz-type inhibitory domains, TFPI inhibits coagulation factor Xa through the K2 domain and factor VIIa-tissue factor complex through the K1 domain. In this way, TFPI blocks the first steps of the extrinsic coagulation pathway.
Tissue Factor Pathway Inhibitor Mechanism
TFPI has been found to block early events in blood coagulation through two distinct mechanisms. The first is the inhibition of TF–factor VIIa by Kunitz domains 1 and 2, which is mediated by TFPIβ on the endothelium. The second is the inhibition of early forms of prothrombinase by Kunitz domain 2 and the C-terminal region of TFPIα released from within platelets.
TFPI interacts with the proteins SON (SON DNA And RNA Binding Protein), SRSF7 (Serine and Arginine Rich Splicing Factor 7), SRSF11 (Serine and Arginine Rich Splicing Factor 11), SAP18 (Sin3A Associated Protein 18), and SMU1 (SMU1 DNA Replication Regulator and Spliceosomal Factor). It has also been shown to interact with Factor X, an enzyme of the coagulation cascade.
Tissue Factor Pathway Inhibitor Structure
TFPI has nine exons that span 70 kb and has a relative molecular mass of 34,000 to 40,000 depending on the degree of proteolysis of the C-terminal region. It’s made up of a negatively charged amino-terminus, three Kunitz domains, and a highly positively charged carboxy-terminus.