Common Pathway of 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
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)
- LMWH (e.g. dalteparin, enoxaparin)
- 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
- Activated by IIa (thrombin)
- 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)
- Heparin
- 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
- Begins with cleavage of Factor X → Xa