Coagulation Cascade

Coagulation Cascade

David Ray Velez, MD

Table of Contents

Coagulation Cascade
Mediators of Platelet Aggregation
Mediators of Anticoagulation

Coagulation Cascade

An Initial Injury Induces Vasoconstriction, Platelet Adhesion, and Thrombin Release

  • Initiates the Intrinsic and Extrinsic Coagulation Pathways

Intrinsic Pathway

  • Initiated By: Exposed Collagen, Pre-Kallikrein, HMW Kininogen
  • Pathway:
    • Activated Factor XII Activates Factor XI
    • Activated Factor XI Activates Factor IX
    • Activated Factor IX and VIII Activates Factor X
  • Associated Factors: Factor 8, 9, 10, 11, and 12

Extrinsic Pathway

  • Initiated By: Tissue Factor (From Trauma and Injured Cells)
  • Pathway:
    • Activated Factor VII Activates Factor X
  • Associated Factors: Factor 7 and 10

Common Pathway

  • Initiated By: Intrinsic or Extrinsic Pathways
  • Prothrombin Complex
    • Components: Activated Factor X, Factor V, Platelet Factor 3, and Prothrombin
    • Converts Prothrombin (Factor II) to Thrombin
  • Thrombin (Factor IIa)
    • Converts Fibrinogen (Factor I) to Fibrin
    • Also Activates Factors V, VIII, and XIII
    • Also Activates Platelets
  • Fibrin (Factor Ia)
    • Links Platelets to Form a Platelet Plug
    • Binds GpIIb/IIIa
  • Fibrin Stabilizing Factor (Factor XIII)
    • Activated by Thrombin
    • Crosslinks Fibrin to Improve Clot Stability

Factor Synthesis

  • Factor VIII is Produced in the Endothelium with vWF
  • All Other Factors are Produced in the Liver
  • Vitamin K Dependent Factors: Factor II, VII, IX, X, Protein C, and Protein S
    • Produced Through Gamma Carboxylation of Glutamate Residues
    • Half-Life of Vitamin K-Dependent Factors:
      • Factor II: 60-72 Hours
      • Factor VII: 4-6 Hours (Shortest)
      • Factor IX: 21-30 Hours
      • Factor X: 48-72 Hours
      • Protein C: 6-8 Hours (Second Shortest)
      • Protein S: 30-60 Hours

Coagulation Cascade 1

Mediators of Platelet Aggregation

Von Willebrand Factor (vWF)

  • Produced by Endothelium
  • Binds to Exposed Collagen at Sites of Vascular Injury for Platelet Adhesion
  • Promotes Platelet Aggregation Through GPIb (Most Efficient When Under Shear Stress)

Thromboxane A2 (TXA2)

  • Produced by Activated Platelets
  • Stimulates Platelet Aggregation
    • Triggers Calcium Release in Platelets (Exposes GpIIb/IIIa Receptor for Fibrin)
  • Also Induces Vasoconstriction

Prostacyclin (PGI2/Prostaglandin I2)

  • Produced by Endothelium
  • Inhibits Platelet Aggregation
    • Increases cAMP in Platelets
  • Also Induces Vasodilation

Mediators of Anticoagulation

Inhibitory Enzymes

  • Antithrombin III (AT-III)
    • Inhibits Thrombin (IIa) and Factor Xa
    • Activated by Heparin
  • Activated Protein C (APC)
    • Degrades Factors Va and VIIIa
  • Protein S
    • Cofactor for Protein C

Fibrinolysis

  • Tissue Plasminogen Activator (tPA)
    • Released from Endothelium
    • Converts Plasminogen to Plasmin
    • Inhibited by Plasminogen Activator Inhibitor (PAI-1 and PAI-2)
  • Plasmin
    • Function:
      • The Most Important Clotting Inhibitor in Plasma
      • Degrades Fibrin (Platelet Plug) into Fibrin Degradation Products
      • Also Degrades Factors V, VIII, and Fibrinogen
    • Plasminogen is Converted to Active Plasmin by tPA, Streptokinase, and Urokinase
    • Inhibited by α-2 Antiplasmin
      • Released from Endothelium
      • Decreased Production in Liver Cirrhosis

Fibrinolysis 2

References

  1. Joe D. Wikimedia Commons. (License: CC BY-SA-3.0)
  2. Jfdwolff . Wikimedia Commons. (License: CC BY-SA-3.0)