4. Physiology
          4.4. Haematology
              4.4.1. Haemostasis
         Clot formation Platelet plug formation

A.1.2. Temporary platelet plug formation

3 stages:

  1. Platelet adhesion
  2. Platelet activation
  3. Platelet aggregation

A.1.2.1. Platelet adhesion

When blood vessel injured
--> Platelet adhere to exposed collagen and vWF via receptors on membrane
--> Binding activates platelets

Adhesion mechanism

2 mechanisms:

  • Adhesion to collagen is facilitated by glycoprotein Ia (on the membrane)
  • Adhesion to vessel wall vWF is by glycoprotein Ib-IX complex (on the membrane)
    * vWF = von Willebrand factor

A.1.2.2. Platelet activation

Platelet activation can be induced by

  • Adhesion to proteins such as collagen, soluble agonist (epinephrine, ADP, serotonin, thrombin)
  • Cell contact during platelet aggregation
  • Platelet-activating factor (PAF)
    * A cytokine secreted by neutrophils, monocytes, and platelets
    * Also has inflammatory activity
    * Acts via G protein-coupled receptor to increase production of arachidonic acid derivatives (including thromboxane A2)

Platelet activation is inhibited by

  • Prostacyclin (PGI2)

Activation results in

  1. Activation of membrane phospholipase A2 and phospholipase C
    --> Various biochemical reactions
    * e.g. Production of thromboxane A2
  2. Reorganisation of cytoskeleton
    --> Platelet transforms from a disc to a sphere with long pseudopods spreading onto subendothelial matrix [PK1:p248]
  3. Release of granules
  4. Exposure of platelet phospholipids
    * aka PF3
    * Provides a surface for assembly of 10ase (i.e. 8a/9a complex) and prothrombinase (i.e. 10a/5a)
    * [HH26:p601]


  • Thromboxane A2
    --> Lowers platelet cAMP
    --> Initiate granule release
    * Also promote vasoconstriction and platelet aggregation
    * [PK1:p248]
    * Also see Endothelium-related vasoactive substances
    * Cyclooxygenase which catalyses the producion of TXA2 is blocked by aspirin

Release of granules

  • Dense granule is released within 30 seconds
    * Serotonin, ADP
    --> Reinforce platelet activation
  • Alpha-granule is released after 30 seconds
    * vWF, fibrinogen, PDGF, etc
    --> Reinforce and mediate platelet aggregation and adhesion

A.1.2.3. Platelet aggregation

Platelet aggregation occurs when platelets encounter:

  • Released thromboxane A2
    --> Platelet aggregation at the site of vascular injury
  • Released ADP
    --> Act on ADP receptors on platelet membrane
    --> Promote platelet to platelet aggregation, and release of more ADP and thromboxane A2
    * i.e. Positive feedback
  • Thrombin
    * Also a potent platelet granule release inducer


  • Platelet-to-platelet aggregation occurs when
    * Fibrinogen or vWF binds to the GPIIb-IIIa complex on platelets
    --> Platelets linked to each other via fibrinogen or vWF

Other notes


  • During platelet plug formation, minute amount of thrombin is produced by tissue factor
    --> Exposes platelet factor 3 (a negatively charged phospholipid)
    * PF3 provides a surface on which vitamin K dependent factors and Ca2+ bind
    * PF3 = platelet phospholipid
  • Very important because of its role in
    * Enhancing platelet adhesion
    * Activating platelets
    * Activating factor 5, 8, 11

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