- Tissue Factor Pathway Inhibitor (TFPI) is located
- On Endothelial Cells (ECs)
- On Monocytes
- In Platelets
- In plasma
- Bulk of TFPI is associated with ECs
- Measurement of low TFPI in plasma doesn’t mean TFPI deficiency
- TFPI associated with ECs → 4X ↑in TFPI upon Heparin injection
- Most of circulating TFPI is bound to lipoproteins & the C terminals are variably degraded
- Physiological Role
- TFPI inhibits FVIIa in a FXa-dependent manner
- TFPI binds to & directly inhibits TF-FVIIa-FXa complex → So, it effectively halts TF initiated activation of coagulation but only after sufficient FXa has been generated to propagate coagulation
- Plasma TFPI has reduced anticoagulant activity
- So, likely not very important anticoagulant role in vivo
- Therapeutic Role
- TFPI binds to Heparan Sulphate on EC surface
- UFH or LMWH displace this bound TFPI → This released TFPI contributes to antithrombotic activities of these drugs
- Isoforms of TFPI
- Two isoforms exist
- TFPIα
- TFPIβ
- TFPIα has 3 Kunitz type protease inhibitory domains → K1, K2, K3
- K1 domain inhibits FVIIa in a FXa dependent manner
- K2 directly binds & inhibits FXa
- Protein S (PS) acts as cofactor in the formation of TFPI-FXa complex
No comments:
Post a Comment