Tissue factor pathway inhibitor
Common pathway · detail · Endothelial Kunitz
A Kunitz-type inhibitor made by endothelium that binds factor Xa and then the TF-VIIa complex, shutting the extrinsic trigger down after only trace amounts of Xa have been produced. Once TFPI has quenched initiation, continued thrombin generation depends entirely on the intrinsic tenase — which is precisely why haemophilia bleeds despite an intact extrinsic pathway.
Traced from the start
Detail
- Source
- Vascular endothelium; most of the circulating pool is lipoprotein-bound and is released into plasma by heparin
- Inhibits
- Factor Xa first, then the resulting Xa-TF-VIIa quaternary complex
- Consequence
- Initiation is self-limiting, making amplification through factors XI, VIII and V obligatory for a durable clot
- Drug target
- Concizumab and marstacimab block TFPI to restore thrombin generation in haemophilia, including in patients with inhibitors
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