Hemostasis and Coagulation Cascade

Overview

• Hemostasis is divided into:
  • Primary Hemostasis: Involves platelet plug formation.
  • Secondary Hemostasis: Involves the coagulation cascade.
• The coagulation cascade is further divided into:
  • Extrinsic Pathway
  • Intrinsic Pathway
  • Common Pathway

Coagulation Cascade

Extrinsic Pathway

• Triggered by tissue injury.
• Tissue Factor: Expressed upon injury; works with factor 7a to activate factor 10 to 10a.

Intrinsic Pathway

• Initiated by exposure to negatively charged surfaces.
• Activation sequence: Factor 12 → Factor 11 → Factor 9 → Factor 8 → Factor 10.

Common Pathway

• Factor 10a and 5a form the prothrombinase complex.
• Thrombin (Factor 2a): Converts fibrinogen to fibrin (Factor 1a).

Calcium's Role

• Important in several steps of the coagulation cascade.

Classical vs. Cell-Based Model

Classical Model

• Useful for coagulation tests and identifying bleeding disorders.

Cell-Based Model

• Initiation: Exposure of tissue factor and interaction with factor 7a, leading to thrombin activation.
• Amplification: Thrombin activates factors 5, 11, and 8.
• Propagation: Formation of intrinsic 10a, prothrombinase complex, and rapid thrombin generation.

Fibrinolysis

• Plasmin: Derived from plasminogen, breaks down fibrin into degradation products like d-dimers.
• Thrombin Activatable Fibrinolysis Inhibitor: Slows fibrinolysis.

Control Mechanisms

Antithrombotic Pathways

1. Protein C and Protein S:
   • Thrombin binds to thrombomodulin, activating protein C.
   • Protein C and S inhibit factors 5a and 8a.
2. Tissue Factor Pathway Inhibitor (TFPI):
   • Inhibits factor 10 activation and tissue factor-factor 7a complex.
3. C1 Esterase Inhibitor:
   • Inhibits factors 11a, 12a, and complement proteases.
4. Antithrombin:
   • Neutralizes thrombin, inhibiting factors 10a and 9a.

Fibrinolysis Control

• Thrombin Activatable Fibrinolysis Inhibitor: Slows fibrin breakdown.
• Plasmin Activator Inhibitor (PAI-1): Inhibits tPA and plasmin formation.
• Alpha2 Antiplasmin: Directly inhibits plasmin activity.

Medication

• Tranexamic Acid: Inhibits tPA, prevents fibrinolysis, used to stop bleeding.

Conclusion

• Reviewed classical and cell-based coagulation models.
• Discussed mechanisms of coagulation control and fibrinolysis.