Overview
This lecture explains the coagulation cascade, focusing on the roles and interplay of the extrinsic and intrinsic pathways, and the central importance of factor 10a.
Vessel Injury and Platelet Activation
- Platelets are the first responders to vessel injury, beginning the sealing process.
- The coagulation cascade is activated at the same time as platelet aggregation.
Coagulation Cascade: Pathways
- The coagulation cascade has two pathways: extrinsic and intrinsic.
- The extrinsic pathway starts when tissue factor from damaged vessels forms a complex with factor 7, activating factor 10.
- The intrinsic pathway involves several coagulation factors activating each other in sequence, leading to a complex that also activates factor 10.
Role of Factor 10a
- Both intrinsic and extrinsic pathways converge at factor 10a.
- Factor 10a is crucial in the cascade, acting as a central activation point.
Thrombin Generation and Fibrin Formation
- Factor 10a, with cofactor 5a, activates thrombin formation.
- A single factor 10a molecule can produce about 1,000 thrombin molecules.
- Thrombin increases platelet activation and stimulates fibrin formation.
- Fibrin creates a mesh that stabilizes arterial and venous clots by trapping cells.
Clinical Relevance
- Because factor 10a is central to clot formation, it is a key target for drugs treating abnormal blood coagulation.
Key Terms & Definitions
- Platelets — Cell fragments that initiate clot formation at injury sites.
- Coagulation Cascade — Series of reactions involving coagulation factors leading to blood clotting.
- Extrinsic Pathway — Coagulation pathway activated by tissue factor and factor 7.
- Intrinsic Pathway — Pathway where coagulation factors activate each other internally.
- Factor 10a — Enzyme where both pathways converge, essential for thrombin generation.
- Thrombin — Enzyme that activates platelets and converts fibrinogen to fibrin.
- Fibrin — Protein forming the structural mesh of a blood clot.
Action Items / Next Steps
- Review diagrams of the coagulation cascade showing where intrinsic and extrinsic pathways converge.
- Study medications targeting factor 10a and their clinical uses.