physiology of coagulation
DESCRIPTION
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, KuwaitTRANSCRIPT
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
AL
CO
AG
UL
AT
ION
CA
SC
AD
E
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