22.22: Extrinsic and Intrinsic Pathways of Hemostasis
Blood clotting or coagulation involves extrinsic and intrinsic pathways, which ultimately merge into the common pathway, forming a fibrin clot.
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which forms a complex with TF upon activation. This TF-Factor VIIa complex then activates Factor X, marking the transition into the common pathway of coagulation.
The Intrinsic Pathway
On the other hand, the intrinsic pathway begins within the bloodstream. It is activated when blood comes into contact with negatively charged surfaces, such as the exposed collagen of a damaged blood vessel. This contact activates Factor XII, triggering a cascade of reactions involving Factors XI, IX, and VIII. Like the extrinsic pathway, the intrinsic pathway also culminates in the activation of Factor X.
Convergence into the Common Pathway
Despite their distinct initiations, the extrinsic and intrinsic pathways converge at the common pathway, beginning with Factor X. This activated Factor X activates the prothrombin activator. This complex acts as a catalyst, converting prothrombin—a protein present in blood plasma—into thrombin.
Thrombin plays a pivotal role in the final steps of clot formation. It transforms fibrinogen, another soluble protein in the blood, into insoluble fibrin strands. These fibrin strands weave together to form a mesh-like network that traps platelets and blood cells, creating a stable and solid clot.
Conclusion
The extrinsic and intrinsic pathways are activated when a blood vessel is injured. The extrinsic pathway is quicker and shorter than the intrinsic pathway, and it usually starts clotting by activating the common pathway first. Essentially, the extrinsic pathway triggers the common pathway to rapidly produce a small amount of thrombin. The intrinsic pathway reinforces this by activating the common pathway to produce more thrombin later.
When blood clotting is stimulated by thrombin generated in the common pathway, it triggers the formation of tissue factor and the release of PF-3 by platelets. These events result in a positive feedback loop that speeds up the clotting process, which is crucial in reducing blood loss after a severe injury. The time taken for clot formation depends on the location and extent of the injury.
