Hemostasis is the biological process that controls bleeding at the site of injured blood vessels. It involves three key steps:
1) Platelet adhesion and activation forms a platelet plug to block blood loss.
2) Coagulation factors in the bloodstream form a fibrin clot over the platelet plug via the intrinsic and extrinsic pathways.
3) The fibrin clot is eventually dissolved by the fibrinolytic system to restore blood flow without risk of hemorrhage. Precise regulation of hemostasis maintains blood fluidity while enabling rapid clot formation in response to vessel injury.
2. • It is a biological or physiological phenomenon
which is responsible tokeep the blood in fluid
state in the circulation as well as to arrest
bleeding followed by an injury to blood vessel.
Defination
3. Objective
To understand how our vascular system keep our blood in its
fluid state.
To know the role of haemostasis components.
To know the biology and mechanism of coagulation.
To know how clot is removed from vascularsystem.
4. To maintain the blood in fluid state while it remains
circulating withinvascular system.
To maintain the integrity of the vessels wall.
To arrest bleeding at the site of injury or blood loss by the
formation of haemostatic plug.
Eventual removal of plug when healing is complete.
Importance of Hemostasis
7. Function of Blood Vessel
Blood vessel with muscular coat help to reduce blood
loss by vasoconstriction.
Blood vessels with a pipe system transport nutrients ,
hormones , gases and other essential factors which are
transported by blood.
8. Endothelial Cell Function
Normal vascular endothelium is a thromboresistant
surface.
Non-thrombogenic- don’t react with plasma or cellular
elements of the blood.
It is antithrombotic. It activates antithrombin III.
When injured (either biologically , chemically or
mechanically) it can profoundly promote hemostasis.
9. ADPase
TM
Thrombin
Antiplatelets Effect:
Inhibition of platelet adhesion, activation and aggregation.
PGI2 (Prostacyclin)-vasodilator and antiplatelet agent.
NO-Nitric Oxide/PGI2
Both bind with the receptors on the platelets and inactivate them. So inhibit platelet
aggregation.
ADPase:
Enzymes that break down the ADP (strong proaggregating agent) released by the
platelets and thus inhibit platelet aggregation.
Destroys
FVa,FVIIIa
Protein
Protein CS
HS
AT-III
Protein Ca
Inhibit
Fxa,FIXa,thrombin
tPA
plasminogen plasmin
fibrinolysis
Endothelial Antithrombotic Mechanism
10. ADPase
TM
Thrombin
Protein C
ProteinS
Protein Ca
Inhibit
Fxa,FIXa,thrombin
AT-III
HS
tPA
plasminogen plasmin
fibrinolysis
Surface expressed integral membrane protein which binds thrombin &results in loss of the
pro-coagulant properties of thrombin.
Thrombin/thrombomodulin complex is a potent anticoagulant complex.
Since it activates protein C to activated-Protein C.
Activated protein C down regulates coagulation by inactivating important proteins
(FVa, FVIIIa)
Destroys FVa,FVIIIa
Thrombomodulin
11. ADPase
TM
Thrombin
Protein C
Heparin sulphate
• Long unbranched polysaccharide expressed at the endothelial
membrane surface.
• Act as a cofactor for the plasma inhibitor antithrombin III.
• Inhibits thrombin and other coagulation factors(FIXa,FXa)
Destroys FVa,FVIIIa
ProteinS
Protein Ca
Inhibit
Fxa,FIXa,thrombin
AT-III
HS
tPA
plasminogen plasmin
fibrinolysis
Binding and Inhibition of Thrombin
12. platelet
GPIb receptor
vWF
Endothelial
cell
subendothelial
collagen
Subendothelial Cell Function
Subendothelium consist of collagen ,elastic
tissues, proteoglycans and non collagenous
glycoproteins {fibronectin, vWF}.
Exposure of this layer after damage of
vessel wall is responsible for platelet
adherence.
vWF bind with collagen, vWF then
undergoes a conformational change and
platelets are captured via their surface
membrane glycoprotein GpIb binding to
vWF.
13. Stages of Hemostasis
Vascular Constriction
Formation of PlateletPlug
Formation of bloodclot
Fibrinolysis
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16. Platelets membrane glycoproteins:
GPIb-IX:
Constitute active receptor for vWF
Mediates vWF dependent adhesion of
platelets to subendothelial
GPIIb/IIIa:
On activation serve to bind fibrinogen
Mediates aggregation
Also receptor forvWF, fibronectin
and thrombospondin
GPIa-IIa:
Constitutively active receptor for collagen.
Mediates platelets adhesion independent of
vWF.
Hemostatic Function
17. Role of Platelets in
Hemostasis
With in 1-2 sec after injury to blood vessel, hemostatic process begins &proceed as
out line bellow:
1.platelet adhesion
2. platelets activation
3. platelets release reaction
4. platelets aggregation
18. Platelets attach to non-platelet surfaces, such as collagen
fibers in the subendothelium.
Platelets move from the blood vessels and into thetissues.
Platelet stick to the exposed collagen underlying damaged
endothelial cells vessel wall.
Platelets Adhesion
19. Platelet activation:
The adhesion of platelets to the vessel
activates them.
Shape change
Aggregation
Release
Clot retraction
Thrombin
Exposed collagen fibres
20. Immediately after adhesion &
activation process of release reaction
or secretion begins.
Platelets activated by adhesion.
Extend projection to make contatct with
each other.
Release thromboxane A2,Serotonin & ADP
activating other platelets.
Serotonin & thromboxane A2 are
varoconstrictors decresing Blood flow
through the injured vessel.ADP causes
stickness.
Platelets Release Reaction
21. ion
Activated Platelets stick together and activated new
Platelets to form a mass called a Platelets plug.
Plug reinforced by fibrin threads formed during
clotting process.
22. Primary haemostasis involves the binding
of platelets to exposed collagen in the sub
endothelium of damaged vessels.
Secondary haemostasis is the process of
activation of coagulation factors leading
to the production of thrombin.
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23. Primary Hemostasis
First physiological response to vascular injury, which is
mediated by platelets, inorder to arrest bleeding
Mechanism:
– Activation of platelets via stimulators such as
thrombin Willebrand Factor (VWF)
– Release of platelet granule products in order to
recruit more platelets to the injured site
24. • Process of blood coagulation
Mechanism:
Coagulation proteins work in concern to generate thrombin
Thrombin converts fibrinogen to fibrin
Fibrin consolidates the platelet plug made in primary hemostasis such
that a thrombus (secondary hemostatic plug) is formed
• Prevents further blood loss from the injury site
Secondary Hemostasis
26. Vasoconstriction
Vasoconstriction is the narrowing of the blood
vessels resulting from contraction of the muscular
wall of the vessels, in particular the
large arteries and small arterioles. The process is
the opposite of vasodilation, the widening of blood
vessels.
30. COAGULATION of blood take place with the help of some proteins called
clotting factors present in plasma.
Clotting factor act as zymogens and under the influence of enzyme are
themselves converted into active enzymes
Roleof Clotting Factors
31. Coagulation factors in the form of zymogens
precursors.
• Ca++ as a co-factor and organizing surface,
Provided by platelets invivo
Provided by a phospholipids emulsion in
vitro
The coagulation process is initiated when
tissue factor - bearing cells are exposed to
blood at a site of injury.
Requirements forCoagulation
32. Fibrinolytic system keep the vascular system free of deposited
fibrin clots.
Essential purpose of fibrinolysis is to digest and solublize the
fibrin, thus restoring potency to occluded vessel.
Fibrinolytic system
35. INHIBITORS
Inhibitors of SerineProteases
Antithrombin
Inhibitor of coagulation having antithrombin activities
Types:
Antithrombin I
Show thrombin adsorbing effect of fibrin
Antithrombin II
Act jointly with heparin act as heparin cofactor
Antithrombin III(alpha 2glycoprotein)
Heparin – inhibit the action of thrombin.
delay the interaction of thrombin and fibrinogen
