A. Clot formation

A.1. Clot formation (in response to injury)

Injury results in 3 (sequential) events
--> Leading to clot formation

1. Constriction of blood vessel
   * Also there is endothelial denudation and loss of inhibitor systems
2. Then formation of temporary plug of platelets
3. Then conversion of the plug into definitive clot
   * Via coagulation cascade

A.1.1. Constriction of blood vessels

... Due to serotonin and other vasoconstrictors (e.g. thromboxane A2, ADP) released from platelets that adhere to the walls of the damaged vessels

NB:

• Thromboxane A2 and ADP also play a role in platelet activation/aggregation
• Endothelin released from damaged endothelium also contribute to vasoconstriction

A.1.2. Temporary platelet plug formation

3 stages

• Platelet adhesion (to vessel walls)
• Platelet activation
• Platelet aggregation

A.1.3. Conversion of plug into definitive clot

Via coagulation cascade

NB:

• Loss of inhibitors of clot formation also contribute to clot formation
  * e.g. Loss of endothelium

A.2. Control of clot formation

• Clot formation is inhibited by:
• Antithrombin III (AT3)
• Heparin cofactor II
• Protein C and protein S
• Tissue factor inhibitor
• Endothelium
• Dilution

Other notes

Role of platelet in coagulation

[Lecture notes]

1. Activates factor 12 in presence of ADP
2. Activates factor 11 in presence of collagen
3. Provides a surface (PF3) for coagulation activity
   * Vitamin K dependent factors (2,7,9,10) and Ca2+ bind to PF3
4. Releases fibrinogen, factor 5, 13
   * May also be involved in factor 8 synthesis
5. Stores vWF
6. ?? Release heparin in neutralising substance (platelet factor 4)
7. Binds to factor 2,8,9,10,11
   --> Activated factors that are bound to platelets are relatively protected from plasma protease inhibitors
8. Binds to fibrinogen, ADP, collagen, vWF
9. Produces thromboxane A2