Contact activation system (factor XII, prekallikrein, high-molecular-weight kininogen)
Trigger · Intrinsic APTT XIIa
Factor XII autoactivates on contact with a negatively charged surface — subendothelial collagen, polyphosphate from platelet dense granules, or glass, kaolin and silica in the APTT tube. Factor XIIa then activates factor XI, which activates factor IX. The system is indispensable in vitro, which is why it sets the APTT, but is largely dispensable in vivo.
Detail
- Components
- Factor XII (Hageman factor), prekallikrein (Fletcher factor), high-molecular-weight kininogen (Fitzgerald factor) and factor XI
- Activators
- Negatively charged surfaces: collagen, platelet polyphosphate, glass, kaolin, silica, ellagic acid, misfolded protein aggregates
- Output
- XIIa activates XI to XIa, which activates IX; XIIa also converts prekallikrein to kallikrein, which liberates bradykinin from HMWK
- Measured by
- APTT — 'partial thromboplastin' is phospholipid without tissue factor, plus a contact activator and calcium
- In vivo
- Thrombin activates factor XI directly, bypassing XII entirely — which is why XI deficiency bleeds and XII deficiency does not
When it goes wrong
Factor XII, prekallikrein or HMWK deficiency
Strikingly prolonged APTT with no bleeding tendency whatever — an incidental finding that must not delay surgery
C1 esterase inhibitor deficiency (hereditary angioedema) removing the brake on kallikrein
Bradykinin-mediated non-pruritic angioedema of face, larynx and bowel, unresponsive to antihistamines, steroids and adrenaline; treat with C1-INH concentrate or icatibant
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