Haemostasis: Role of Platelets Flashcards
What are Platelets mechanism of action?
Rapidly adhere to site of injury and to each other leading to formation of platelet plug
What leads to the formation of fibrin?
Activation of parallel clotting factors
What two components seal off the wound?
Aggregated platelets and fibrin
What are platelets derived from?
Megakaryocytes in bone marrow
What do platelets not contain?
Nucleus
What increases platelets surface area?
Open canalicular system (OCS)
What do platelets’ dense granules contain?
Serotonin, ADP and Ca2+
What do platelets alpha granules contain?
Proteins
What does the Golgi of the platelets provide evidence for?
Ongoing protein synthesis
What do platelets bind to?
Collagen and other matrix molecules
When is collagen exposed?
When vessel wall is injured
What are 2 collagen receptors?
GPIb/V/IX
GPVI
What does GPIb/V/IX need to attach to collagen?
von Willebrand factor (VWF)
What does the GPIb/V/IX-VWF-collagen interaction allow for?
Binding of platelets to vessel wall in high shear conditions eg. arteries
What does GPVI allow for?
Direct binding of platelets
What triggers release of alpha and dense granules?
Collagen receptor signalling
What is the role of ADP?
Potent platelet activator
Produces surfaces for effective clotting - stimulates further platelet activation
What synthesis does platelet activation lead to?
Thromboxane A2 (TXA2) synthesis
What does platelet binding to TXA2 receptors cause?
Further activation
What does vessel wall injury induce?
Clotting cascade -> production of thrombin
What thrombin receptors do platelets have?
Protease activated receptors (PARs)
What does PAR activation contribute to?
Amplification of platelet activation
What do activated platelets contain?
Intergrin (alpha II and beta 3)
What does intergrin cause?
Inside out signalling leads to fibrinogen binding
What does fibrinogen binding result in?
Crosslinking of platelets and formation of platelet plug
What inhibits platelet activation?
Endothelial cells
What 3 ways do ECs inhibit platelet activation?
- ADP-degrading enzyme at cell surface (Ecto ADPase)
- Prostacyclin release - binds to G protein coupled receptor on platelet which inhibits cAMP signalling
- NO release induces synthesis of cGMP
