Coagulation Cascade: Overview and Key Concepts

What is the Coagulation Cascade?

• Coagulation Cascade: A series of steps responding to bleeding from tissue injury, resulting in blood clot formation.
• Hemostasis: Derived from "hem" (blood) and "stasis" (to stop), referring to the process of stopping bleeding.
• Phases of Hemostasis:
  • Primary Hemostasis: Formation of an unstable platelet plug at the injury site.
  • Secondary Hemostasis (Coagulation Cascade): Stabilizes the plug to stop blood flow and allow tissue repair.

Mechanism of Coagulation Cascade

• Involves activation of clotting factors, proteins essential for blood clotting.
• Clotting factors are serine proteases, enzymes that accelerate protein breakdown.
• Factors exist initially as inactive zymogens and become activated in sequence.

Pathways in Coagulation

1. Extrinsic Pathway

• Initiated by factor III (tissue factor) interacting with factor VII.
• Activated upon endothelial tissue injury, exposing tissue factor to blood.

2. Intrinsic Pathway

• Involves factors XII, XI, IX, and VIII.
• Begins when factor XII is exposed to collagen, kallikrein, and HMWK.

3. Common Pathway

• Begins with the activation of factor X.
• Formation of prothrombinase complex leading to conversion of prothrombin to thrombin.
• Thrombin converts fibrinogen into fibrin, forming a stable clot.

Fibrin Production

• Fibrin (factor Ia) forms at the end of the cascade, converting fibrinogen into fibrin to stabilize the clot.

Main Goal of Coagulation

• To form a stable blood clot, preventing bleeding and allowing tissue repair.

Coagulation Disorders

• Disorders affecting the coagulation cascade can result in excessive or inadequate clotting.
• Common disorders include:
  • Von Willebrand Disease: Deficiency in von Willebrand factor due to genetic mutation.
  • Hemophilia: Genetic mutations causing deficiencies in clotting factors VIII (Hemophilia A), IX (Hemophilia B), XI (Hemophilia C).
  • Vitamin K Deficiency: Impairs activation of factors II, VII, IX, X, affecting all pathways.

Important Facts

• Coagulation involves intrinsic, extrinsic, and common pathways.
• Both pathways ultimately lead to factor X activation, proceeding to fibrin formation for clot stabilization.
• Common coagulation disorders often involve deficiencies in specific clotting factors, prominently hemophilia and vitamin K deficiency.

References

• Arruda V.R., & High K.A. (2018). Coagulation disorders. In Harrison's Principles of Internal Medicine (20th ed.). McGraw-Hill.
• Levi M (2021). Control of coagulation reactions. In Williams Hematology (10th ed.). McGraw-Hill.
• Palta, S., Saroa, R., & Palta, A. (2014). Overview of the coagulation system. Indian journal of anaesthesia, 58(5), 515–523.
• Kumar, V., Abbas, A., & Aster, J. (2014) Red Blood Cell and Bleeding Disorders. In Robbins & Cotran Pathologic Basis of Disease (9th ed.). Elsevier.