Overview
This lecture covers the coagulation cascade, outlining its pathways, key steps, end products, and related disorders that affect blood clotting.
Introduction to Coagulation Cascade
- The coagulation cascade is a series of steps triggered by tissue injury to produce a stable blood clot.
- Hemostasis is the process of stopping bleeding, with primary hemostasis forming a platelet plug and secondary hemostasis stabilizing it.
Pathways of the Coagulation Cascade
- There are three interconnected pathways: extrinsic, intrinsic, and common.
- The extrinsic pathway starts with tissue factor (factor III) exposure and activation of factor VII; it requires vitamin K.
- The intrinsic pathway is triggered by factor XII contacting collagen and involves factors XII, XI, IX, and VIII.
- Both pathways activate factor X, leading into the common pathway.
Common Pathway and Clot Formation
- In the common pathway, factors Xa, Va, and calcium form a prothrombinase complex that converts prothrombin (II) to thrombin (IIa).
- Thrombin converts fibrinogen (I) to fibrin (Ia) and activates factor XIII, which crosslinks fibrin to stabilize the clot.
- Thrombin also helps activate platelets and factors V, VIII, and IX.
Fibrin Production and Clot Stabilization
- Fibrin is produced at the cascade's end by thrombin-mediated cleavage of fibrinogen.
- Fibrin forms a mesh that stabilizes the blood clot.
Coagulation Disorders
- Coagulation disorders result from deficiencies in clotting factors, causing too much or too little clotting.
- Von Willebrand disease (deficiency in von Willebrand factor) mainly affects primary hemostasis and stabilizes factor VIII.
- Hemophilia A (factor VIII deficiency), B (factor IX deficiency), and C (factor XI deficiency) disrupt the intrinsic pathway.
- Vitamin K deficiency impairs production of factors II, VII, IX, and X, affecting all pathways.
Key Terms & Definitions
- Hemostasis — process to stop bleeding.
- Clotting Factor — protein involved in forming a blood clot.
- Zymogen — inactive form of an enzyme, such as clotting factors.
- Thrombin (IIa) — enzyme that converts fibrinogen to fibrin.
- Fibrin (Ia) — protein forming the meshwork of a blood clot.
- Intrinsic Pathway — clotting triggered by factors inside blood.
- Extrinsic Pathway — clotting triggered by tissue factor outside blood.
- Common Pathway — final steps leading to clot formation.
Action Items / Next Steps
- Review diagrams and sequential steps of the coagulation pathways.
- Memorize the key clotting factors for each pathway and their order.
- Understand the clinical relevance of major coagulation disorders.