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

2. 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

3. Primary Hemostasis
Initiated within seconds.
Short lived.
Results in a soft platelet plug to seal the breach
in the vessel wall.

4. Primary Hemostasis
Step 1: Local Vasoconstriction

5. Step 2: Platelet adhesion and formation of soft platelet plug
Primary Hemostasis

6. Secondary Hemostasis
Platelet
Membrane
Coagulation
Factors
Co-factors

7. Role of Vitamin K
Vitamin K
Oxido-
Reductase
γ-Carboxylation

8. Evolution of Coagulation Theories

9. Both pathways are initiated independently
and
Unite only at Factor X (FX) and Factor V (FV) level
CLASSICALCOAGULATIONCASCADE

10. Pitfalls in cascade model

11. 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.

12. Differences in these models

13. Cell Based Model of Coagulation
Initiation
[TF Cell]
Amplification
[Platelet]
Propagation
[Active Platelet]
Stabilization
of Clot
Inhibition of
Further
Coagulation
Five Steps
Two Cells

14. What is Tissue Factor?

15. Initiation
TF-VIIa Complex
Activation of FX & FIX:
FXa & FVa convert small amount
of Prothrombin to Thrombi

16. Amplification
1
2
3

17. Propagation
THROMBIN

18. Clot formation
XIII
aXIII
Fibrinogen Fibrin monomer
Cross-linked mesh
Inactive Platelet Activated Platelet

19. Result !!

20. 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

21. 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

22. 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

23. 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