Physiology of Hemostasis

Presenter: Andrew Wolf

Introduction

• Hemostasis involves pathways leading to clot formation.
• Two mechanisms of injury:
  • Intrinsic (inside the vessel)
  • Extrinsic (damage to vessel/tissues)
• Both systems often work concurrently in reality.

Intrinsic Pathway

Platelet Plug Formation

• Occurs inside an intact vessel.
• Involves platelet activation and aggregation.
• Key Elements:
  • Platelets are cell fragments with spinous processes.
  • Activated by von Willebrand factor (VWF) secreted by damaged endothelial cells.
  • VWF makes platelets sticky, forming a plug.
  • Fibrinogen: Binds with platelets, forming cross-linkages, remains inactive initially.

Activation of Intrinsic Pathway

• Triggered by exposure of blood to basement membrane due to vessel injury.
• Key Steps:
  • Collagen activates coagulation factor 12 (Hageman factor) to 12A.
  • Sequence of activations occur (12A -> 11A -> 9A -> 10A -> thrombin -> fibrin).
  • Fibrin polymerizes to form a stable mesh.

Extrinsic Pathway

• Initiated by damage to tissues or vessels, activating tissue factor (factor 3).
• Tissue Factor Locations:
  • Inside cells
  • On some cell membranes
  • In extracellular fluid

Activation of Extrinsic Pathway

• Triggered by:
  • Inflammatory cytokines
  • Cell injury
  • Blood in tissue
• Process:
  • Tissue factor activates factor 7 to 7A.
  • 7A activates factor 10 to 10A (common with intrinsic pathway).
  • Leads to common pathway cascade.

Common Pathway

• Steps:
  • 10A converts prothrombin to thrombin.
  • Thrombin cleaves fibrinogen to fibrin.
  • Fibrin forms long polymer strands, creating a weave with 13A.

Importance and Complexity

• Many steps for amplification of response.
• Intrinsic pathway less critical for hemostasis but critical in thrombosis.
• Absence of Hageman factor has minimal bleeding impact, underscoring extrinsic pathway importance.

Conclusion

• Detailed exploration of hemostasis and coagulation cascade.
• Next video will cover factors controlling coagulation.
• Feedback and questions are encouraged.

Next Steps

• Watch upcoming videos on controlling the coagulation cascade.