Hemostasis involves vascular constriction, platelet plug formation, and blood clot formation to prevent blood loss after a vessel rupture. There are two pathways for blood clot formation - the intrinsic pathway which begins with blood trauma, and the extrinsic pathway which begins when traumatized tissue contacts blood. Clot formation involves a cascade of coagulation factors culminating in thrombin converting fibrinogen to fibrin to form a clot. The clot is later dissolved by plasmin in a process called fibrinolysis. Hemostasis is prevented from occurring inappropriately through factors on intact endothelial cells and actions of antithrombin and heparin which inhibit thrombin and other coagulation factors.

1. REGULATION OF HEMOSTASIS

2. HEMOSTASIS?
1. Hemostasis = prevention of blood loss
2. When there is vessel ruptures, hemostasis is
achieved by:
• Vascular constriction
• Platelet plug formation
• Blood clot formation
• Fibrous tissue growth or dissolution

3. Vascular Constriction
When the blood vessels rupture, the vessels
contract by:
1. Myogenic spasm
2. Local autacoid factors (local mediators) from
traumatized tissue
3. Nervous reflexes by pain nerve impulses
initiation
4. Vasoconstrictor substances from platelets eg.
Thromboxane A2

4. Platelet Plug Formation
Platelets come in
contact with
subendothelial
collagen
Platelet aggregation The activation of
and formation of platelet (formation
platelet plug of pseudopods to
become sticky)
Secretion of multiple
ADP & Thromboxane
active factors eg.
A2 activate nearby
ADP & Thromboxane
platelets
A2

5. Blood Clot Formation
Two pathways:
1. Extrinsic pathway: begins when traumatized
vascular wall or traumatized extravascular
tissues that come in contact with the blood
2. Intrinsic pathway: begins with trauma to the
blood itself or exposure of the blood to
collagen from a traumatized blood vessel wall

6. Extrinsic
pathway
Tissue factor aka Thromboplastin
Thromboplastin + VIIa + Ca2+
activate factor X
Xa + Va + Thromboplastin + Ca2+
becomes prothrombin activator
complex
Prothrombin activator complex +
platelet phospholipid + Ca2+
 activate prothrombin

7. Intrinsic pathway
Blood trauma causes activation of
XII and platelet activation to
release platelet phospholipids
VIII VIIIa
IXa + VIIIa + Platelet phospholipid +
Ca2+ Thrombi
 Activate factor X n

8. Fibrin Formation
Factor XIII aka
fibrin stabilizing factor
Thrombin
Fibrin
Fibrinogen
monomer
Factor XIIIa aka
activated fibrin
stabilizing factor
Fibrin fibre

9. Dissolution
tissue plasminogen
activator (t-PA)
released by
endothelium
Plasminogen aka Plasmin aka
profibrinolysin fibrinolysin
Digest fibrin fibres, fibrinogen, Factor
V, Factor VIII, prothrombin, and
Factor XII

10. Prevention of Clotting
1. Endothelial surface factors
• Smoothness of vascular wall  prevent intrinsic
pathway activation
• Glycocalyx layer that repels clotting factors and
platelets
• Thrombomodulin (on endothelial surface) which:
bind to thrombin  prevent coagulation
activates protein C inactivate Va and VIIIa

11. Prevention of Clotting
2. Antithrombin action of fibrin and
antithrombin
• Thrombin are adsorbed into fibrin mesh and
prevent further coagulation
• Unadsorbed thrombin binds to antithrombin
and inactivates it

12. Prevention of Clotting
3. Heparin action
• Heparin released by mast cells and basophils.
• It enhances the antithrombin action and more
• The heparin-antithrombin complex removes
other activated factors eg. XIIa, XIa, Xa, IXa