Common Pathway of Coagulation

Summary

The common pathway of coagulation is the set of final steps needed to form a blood clot, shared in common by both the extrinsic and intrinsic starting pathways. This common pathway starts with the cleavage and activation of factor X by either the intrinsic or extrinsic pathway, in a process that requires calcium, phospholipids from a membrane, and vitamin K.  Next, Factor V is independently cleaved and activated by Factor II, in a process that is inhibited by Proteins C and S. The resulting activated factors V and X then combine to form a complex, and this complex in turn activates Factor II. Factor II has a few other names as pro-thrombin in its unactivated state, and thrombin in its activated form. The activation of factor 2 also requires calcium, phospholipids from a membrane, and vitamin K to be present. Activated factor 2 then goes onto cleave and activate factor 1. Factor 1 is also known as fibrinogen in its unactivated state, and fibrin in its activated form. This fibrin then accumulates and forms a mesh. This fibrin mesh stabilizes a platelet plug, which formally marks the formation of a blood clot. Notably, the fibrin in this mesh is stabilized by factor XIII.

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