Coagulation Pathways and Factors
Coagulation is the process by which blood forms clots to stop bleeding after an injury. There are two main coagulation pathways – the intrinsic pathway and the extrinsic pathway. Both pathways lead to a common pathway that results in fibrin formation and blood clotting.
The intrinsic pathway is initiated by exposure of blood to negatively charged surfaces. It involves factors XII, XI, IX, VIII, X, V, II (prothrombin), and I (fibrinogen …. . . . . . . . .
Coagulation is the process by which blood forms clots to stop bleeding after an injury. There are two main coagulation pathways – the intrinsic pathway and the extrinsic pathway. Both pathways lead to a common pathway that results in fibrin formation and blood clotting.
Before we talk about the pathways lets know the Factors that control the coagulation cascade
There are 13 Factors that contribute in the coagulation Process
– Factor I: Fibrinogen – Inactive protein converted into fibrin to form blood clots
– Factor II: Prothrombin – Inactive enzyme converted into active thrombin to convert fibrinogen into fibrin
– Factor III: Tissue Factor – Activates extrinsic pathway by binding factor VII
– Factor IV: Calcium – Ion required for functioning of factors IX, X and prothrombin
– Factor V: Proaccelerin – Accelerates conversion of prothrombin to thrombin
– Factor VII: Proconvertin – Activates factor X with tissue factor to initiate extrinsic pathway
– Factor VIII: Antihemophilic Factor A – Accelerates activation of factor X by binding factor IXa in intrinsic pathway
– Factor IX: Christmas Factor – Activates factor X in presence of factor VIIIa and calcium in intrinsic pathway
– Factor X: Stuart-Prower Factor – Activated by intrinsic or extrinsic pathways to convert prothrombin to thrombin
– Factor XI: Plasma Thromboplastin Antecedent – Activates factor IX in intrinsic pathway, activated by factor XII
– Factor XII: Hageman Factor – Activates factor XI when blood contacts negatively charged surfaces
– Factor XIII: Fibrin-Stabilizing Factor – Stabilizes fibrin clots by crosslinking fibrin strands, activated by thrombin
– Von Willebrand Factor: Von Willebrand Factor – Binds platelets and carries factor VIII in blood circulation
These coagulation factors work in a cascade to amplify coagulation signals, generate thrombin, and convert fibrinogen to fibrin to form blood clots and stop bleeding after injury.
Coagulation Pathways
There are 3 Coagulation Pathways
1. Intrinsic Pathway
The intrinsic pathway initiates coagulation in response to contact with negatively charged surfaces. It does not rely on exposed tissue factor. The pathway involves multiple feedback loops that amplify the coagulation response.
The steps are:
- Contact activation – Factor XII is activated when blood is exposed to negatively charged surfaces such as collagen, activating the intrinsic pathway.
- Factor XIIa activates factor XI into factor XIa.
- Factor XIa activates factor IX into factor IXa.
- Factor IXa binds to factor VIIIa on phospholipid surfaces, forming the tenase complex.
- The tenase complex activates factor X into factor Xa.
- Factor Xa associates with factor Va to form the prothrombinase complex.
- Prothrombinase converts prothrombin to thrombin.
- Thrombin converts fibrinogen to fibrin, forming clots.
This pathway takes longer to initiate clotting compared to the extrinsic pathway. However, the series of positive feedback loops greatly amplifies the coagulation response. The intrinsic pathway is important for clot formation in the absence of tissue factor and for sustaining coagulation over time. It helps limit bleeding from damaged vessels.
2. Extrinsic Pathway
The extrinsic pathway initiates coagulation after tissue injury and vessel damage. It relies on tissue factor, which is expressed by cells outside the circulatory system.
The steps are:
1. Tissue injury causes exposure of tissue factor (TF) from cells in the damaged tissue. TF is a transmembrane protein that is normally separated from blood.
2. Circulating factor VII binds to TF, forming a TF-VIIa complex. The binding activates factor VII.
3. The TF-VIIa complex catalyzes the conversion of factor X to its active form Xa.
4. Factor Xa associates with activated factor V on phospholipid surfaces to form the prothrombinase complex.
5. The prothrombinase complex converts prothrombin to thrombin.
6. Thrombin converts fibrinogen into fibrin monomers which polymerize into fibrin fibers.
7. Activated factor XIII crosslinks the fibrin fibers to stabilize the clot.
The extrinsic pathway is initiated by tissue factor exposure after injury. This leads to activation of factors X, V, and prothrombin to generate thrombin. Thrombin converts fibrinogen to fibrin to form the blood clot. This rapid initiation helps quickly seal wounds and stop bleeding after trauma.
3. Common Pathway
The common pathway refers to the final steps of coagulation that are shared between the intrinsic and extrinsic pathways. The common pathway results in the formation of a fibrin clot.
The steps are:
1. Formation of the prothrombinase complex
– Active factor Xa combines with factor Va and calcium on a phospholipid surface provided by platelets. This forms the prothrombinase complex.
2. Conversion of prothrombin to thrombin:
– The prothrombinase complex converts the inactive zymogen prothrombin into the active enzyme thrombin.
3. Conversion of fibrinogen to fibrin:
– Thrombin cleaves fibrinogen to form fibrin monomers. The fibrin monomers then combine to form strands of fibrin.
4. Crosslinking of fibrin:
– Factor XIII is also activated by thrombin. Activated factor XIII crosslinks the fibrin strands to stabilize the clot.
5. Inhibition of fibrinolysis:
– Thrombin activates a protein called TAFI (thrombin activatable fibrinolysis inhibitor). TAFI inhibits the breakdown of fibrin clots.
The common pathway involves the activation of prothrombin to thrombin, followed by the formation and stabilization of fibrin strands to form the final blood clot. The end result is a crosslinked fibrin clot that is resistant to breakdown. This pathway is essential for effective hemostasis after vascular injury.