Download - Physiology of Coagulation
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
Primary Hemostasis
Initiated within seconds.
Short lived.
Results in a soft platelet plug to seal the breach
in the vessel wall.
Primary Hemostasis
Step 1: Local Vasoconstriction
Step 2: Platelet adhesion and formation of soft platelet plug
Primary Hemostasis
Secondary Hemostasis
Platelet Membrane
Coagulation Factors
Co-factors
Role of Vitamin K
Vitamin K Oxido- Reductase
γ-Carboxylation
Evolution of Coagulation Theories
Both pathways are initiated independently and
Unite only at Factor X (FX) and Factor V (FV) level
CL
AS
SIC
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CO
AG
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AT
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CA
SC
AD
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Pitfalls in cascade model
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.
Differences in these models
Cell Based Model of Coagulation
Initiation
[TF Cell]
Amplification
[Platelet]
Propagation [Active Platelet]
Stabilization
of Clot
Inhibition of Further
Coagulation
Five Steps Two Cells
What is Tissue Factor?
Initiation
TF-VIIa Complex
Activation of FX & FIX: FXa & FVa convert small amount of Prothrombin to Thrombi
Amplification
1
2
3
Propagation
THROMBIN
Clot formation
XIII aXIII
Fibrinogen Fibrin monomer Cross-linked mesh
Inactive Platelet Activated Platelet
Result !!
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
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
Fibrinolysis R
ED
: S
UP
RE
SS
ES
BL
UE
: A
CC
EL
ER
AT
ES
Tissue Plasminogen
Activator [tPA]
α2 Antiplasmin Α2 Macroglobulin
Plasminogen Activator Inhibitor 1&2
Thrombin Activatable Fibrinolysis Inhibitor
Factor XIa, XIIa, Kallikrein
Urokinase
THROMBIN
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