Medicine & USMLE

Common 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

  • Common Pathway of Coagulation
    • Common endpoint of both the intrinsic and extrinsic pathways
    • Pathway
      • Begins with cleavage of Factor X → Xa
        • Via intrinsic or extrinsic pathway
        • Requires calcium (Ca2+), phospholipid
        • Vitamin K-dependent clotting factor
          • Inhibited by Warfarin
        • Factor Xa blocked by anticoagulants
          • LMWH (e.g. dalteparin, enoxaparin)
            • stronger activity at Xa than IIa
          • Heparin
            • equal activity at Xa and IIa
          • Direct Xa inhibitors (e.g. apixaban, edoxaban)
          • Fondaparinux (synthetic factor Xa inhibitor)
      • Independent cleavage of Factor V → Va
        • Activated by IIa (thrombin)
          • Does not rely on Factor Xa; acts as an independent co-factor
          • Binds to platelets and is activated by thrombin
        • Degraded by proteins C & S
          • Factor V is mutated in Factor V Leiden (causes thrombophilia), which reduces susceptibility to degradation by protein C
      • Factors Xa + Va stimulates cleavage of Factor II (prothrombin) → IIa (thrombin)
        • Requires calcium (Ca2+), phospholipid
        • Vitamin K-dependent clotting factor
          • Inhibited by Warfarin
        • Factor IIa activity blocked by anticoagulants
          • Heparin
            • equal activity at Xa and IIa
          • LMWH (e.g. dalteparin, enoxaparin)
            • stronger activity at Xa than IIa
          • DTIs (e.g. argatroban, bivalirudin, dabigatran)
        • Factor IIa activity measured by thrombin time (TT)
      • Factor IIa (thrombin) stimulates cleavage of Factor I (fibrinogen)  Ia (fibrin)
      • Fibrin aggregates → forms fibrin mesh
        • Fibrin mesh stabilizes platelet plug to form blood clot
        • Fibrin is stabilized by Factor XIIIa (whose formation from XIII is also stimulated by IIa)
          • Factor XIIIa is known as fibrin stabilizing factor