Intrinsic Pathway of Coagulation
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Coagulation
- Common Pathway of Coagulation
- Extrinsic Pathway of Coagulation
- Intrinsic Pathway of Coagulation
- Hemophilia A
- Hemophilia B
- Hemophilia C
- Factor V Leiden
- Antithrombin-3 Deficiency
Summary
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Key Points
- Intrinsic Pathway of Coagulation
- Also known as the contact activation pathway
- Pathway
- Starts with contact with a damaged vessel surface
- Collagen
- Usually sub-endothelial collagen exposed by vessel injury
- Basement membrane
- This is made of type 4 collagen, so this is effectively the same thing as the above
- Activated platelets
- via polyphosphate
- Activating lab compounds (above)
- Collagen
- Activates Factor XII (Hageman Factor) by cleavage → XIIa
- Inhibited by C1-esterase inhibitor
- Factor XIIa cleaves Factor XI → XIa
- Also inhibited by C1-esterase inhibitor
- Factor XI is deficient in Hemophilia C
- Factor XIa cleaves Factor IX → IXa
- Requires calcium (Ca2+), phospholipid
- Vitamin K-dependent clotting factor
- Inhibited by Warfarin
- Stimulated by Factor IIa (downstream)
- Factor IX is deficient in Hemophilia B
- Independent cleavage of Factor VIII → VIIIa
- Activated by IIa (thrombin)
- Does not rely on factor IXa, activated in an independent fashion by thrombin
- Factor VIII is deficient in Hemophilia A
- Factor VIII is stabilized by vWF
- vWF is a protective carrier protein for Factor VIII; without which it is quickly cleared from the bloodstream
- Factor VIII activity may be deficient in von Willebrand disease
- Blocked by proteins C & S
- Activated by IIa (thrombin)
- Factors VIIIa + IXa stimulates cleavage of Factor X → Xa
- Entry into common coagulation pathway
- Starts with contact with a damaged vessel surface
- Monitoring
- PTT / aPTT (activated partial thromboplastin time)
- Measures intrinsic and common pathway (time to clot) after adding an intrinsic activator (silica, celite, kaolin, or ellagic acid)
- Usually used to monitor therapeutic effect of heparin, although warfarin use may also increase PTT levels (however, vitamin K-dependent clotting factor with the shortest half-life is factor VII, which is not involved in intrinsic pathway)
- Mnemonic: “play table tennis outside” = PTT inside
- PTT / aPTT (activated partial thromboplastin time)