Physiology of Coagulation

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This lecture was the opening lecture on the ‘Physiology of Coagulation’ at the Continuing Medical Education (CME) Grand Rounds, 2011. Organised by Kuwait Anesthesia Council, Kuwait

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Physiology of Coagulation

  1. 1. Introduction  Coagulation is a complex process by which blood forms clots.  An important part of hemostasis.  The process is described in 2 steps:  PRIMARY  SECONDARY
  2. 2. Primary Hemostasis Initiated within seconds. Short lived. Results in a soft platelet plug to seal the breach in the vessel wall.
  3. 3. Primary Hemostasis Step 1: Local Vasoconstriction
  4. 4. Step 2: Platelet adhesion and formation of soft platelet plug Primary Hemostasis
  5. 5. Secondary Hemostasis Platelet Membrane Coagulation Factors Co-factors
  6. 6. Role of Vitamin K Vitamin K Oxido- Reductase γ-Carboxylation
  7. 7. Evolution of Coagulation Theories
  8. 8. Both pathways are initiated independently and Unite only at Factor X (FX) and Factor V (FV) level CLASSICALCOAGULATIONCASCADE
  9. 9. Pitfalls in cascade model
  10. 10. Cell Based Model of Coagulation D. Monroe M. Hoffman Proposal  The cascade is a biochemical model.  NOT a true reflection of what happens in the body.
  11. 11. Differences in these models
  12. 12. Cell Based Model of Coagulation Initiation [TF Cell] Amplification [Platelet] Propagation [Active Platelet] Stabilization of Clot Inhibition of Further Coagulation Five Steps Two Cells
  13. 13. What is Tissue Factor?
  14. 14. Initiation TF-VIIa Complex Activation of FX & FIX: FXa & FVa convert small amount of Prothrombin to Thrombi
  15. 15. Amplification 1 2 3
  16. 16. Propagation THROMBIN
  17. 17. Clot formation XIII aXIII Fibrinogen Fibrin monomer Cross-linked mesh Inactive Platelet Activated Platelet
  18. 18. Result !!
  19. 19. Inhibitors of Coagulation • Inhibition of the TF-VIIa complex. • Binds to directly inactivate thrombin as well as the factors (IXa, Xa, and XIa). • Catalyses:Plasminogen  Plasmin
  20. 20. Inhibitors of Coagulation • Protein C is activated when thrombin binds to thrombomudulin. • Protein S boosts the activity of Protein C. • Jointly, they inactivate Factor Va & VIIIa. • Plasmin degrades fibrin strands. Prevents build-up of excess clot. Fibrinolytic System
  21. 21. Fibrinolysis RED:SUPRESSES BLUE:ACCELERATES Tissue Plasminogen Activator [tPA] α2 Antiplasmin Α2 Macroglobulin Plasminogen Activator Inhibitor 1&2 Thrombin Activatable Fibrinolysis Inhibitor Factor XIa, XIIa, Kallikrein Urokinase THROMBIN
  22. 22. Injury to vessel Platelet activation by contact to endothelium & subendothelium, →formation of Platelet Plug Coagulation pathway Activation → generation of thrombin & fibrin clot → Platelet Plug Stabilization Fibrinolysis & Clot Removal Control of clot extension by antithrombotic mechanisms Healing & Repair of injury

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