Medicine & USMLE

Intrinsic Pathway of Coagulation

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Coagulation
  1. Common Pathway of Coagulation
  2. Extrinsic Pathway of Coagulation
  3. Intrinsic Pathway of Coagulation
  4. Hemophilia A
  5. Hemophilia B
  6. Hemophilia C
  7. Factor V Leiden
  8. 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)
      • 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
      • Factors VIIIa + IXa stimulates cleavage of Factor X → Xa
        • Entry into common coagulation pathway
    • 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