Tissue factor and the extrinsic trigger
Trigger · Factor III Extrinsic PT / INR
Tissue factor (factor III) is a transmembrane protein expressed constitutively by subendothelial fibroblasts, pericytes and vascular smooth muscle, and induced on monocytes and endothelium by endotoxin and cytokines. A breach in the vessel wall exposes it to plasma factor VII, and this — not contact activation — is how coagulation actually begins in vivo.
Detail
- Also called
- Factor III, thromboplastin, CD142
- Where
- Constitutive on subendothelial fibroblasts, pericytes and vascular smooth muscle; brain, lung and placenta are especially rich; induced on monocytes and endothelium by endotoxin, TNF and IL-1
- Binds
- Factor VII/VIIa to form the TF-VIIa (extrinsic tenase) complex on an anionic phospholipid surface with Ca2+
- Measured by
- The prothrombin time — the reagent is recombinant or tissue-derived thromboplastin plus calcium
- Restrained by
- Tissue factor pathway inhibitor from endothelium, which quenches TF-VIIa after only trace factor Xa has been generated
When it goes wrong
Endotoxin and cytokines inducing monocyte and endothelial tissue factor in Gram-negative sepsis
Systemic thrombin generation: disseminated intravascular coagulation with microvascular thrombosis, consumption of platelets and fibrinogen, and simultaneous bleeding
Tissue factor released from brain, placenta, amniotic fluid or adenocarcinoma mucin
Head injury, amniotic fluid embolism, placental abruption and mucin-secreting cancers all precipitate DIC; Trousseau syndrome is migratory thrombophlebitis in an occult adenocarcinoma
Atherosclerotic plaque rupture exposing the tissue-factor-rich lipid core
Occlusive platelet-fibrin thrombus and acute myocardial infarction
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