Common Pathway of Coagulation

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