Platelet activation - Haemostasis - BB Flashcards
Which hormone regulates the production of platelets:
TPO - thrombopoietin
Glycoprotein produced mostly in the liver
Mechanisms of activating platelets:
- endothelial injury (direct)
2. stimuli from other activated platelets (indirect)
Mechanisms of activating platelets:
- endothelial injury (direct)
2. stimuli from other activated platelets (indirect)
Where is vWF synthesised and storred?
synthesised by endothelial cells and megakaryocytes
Stored in:
- Weibel-Palade bodies in endothelial cells
- Alpha granules in platelets
some found in the plasma
vWF release:
From alpha-granules - when platelets are activated
From weibel-palade bodies - when endothelial cells are damaged
Roles of vWF (x3)
- Carrier protein for VIII - [released in presence of thrombin]
- Binds platelets to damaged endothelium (adhesion)
- Binds activated platelets together (aggregations)
Platelet adhesion (1/3)
Vascular damage - leads to exposure of collagen
Subendothelial collagen binds to vWF
vWF binds to GP1b receptor on platelets
Platelet aggregation: (2/3)
Mediated by GPIIb/IIIa surface receptor
Platelet activation causes these surface receptors to change conformation and they become capable of binding
ACTIVE GPIIb/IIIa - binds to either fibrinogen or to vWF
Intermediates for platelet aggregation
GPIIb/IIIa can bind either fibrinogen or vWF
Platelet secretion: (3/3)
Platelets are activated either by:
- binding to subendothelial collagen
- stimulation by activating substances (released from other platelets)
2 types of granules - Alpha and dense
Contents of platelet alpha granules:
(most abundant)
Fibrinogen
vWF
Platelet factor 4
Contents of platelet Dense granules
ADP - activates other platelets
Calcium - for coag cascade
Serotonin
HIT
Heparin induced thrombocytopenia
Rare life threatening effect of heparin administration
Antibodies are formed agaisnt PF4 complexed with heparin
- – Causing platelet activation
- – and diffuse thrombosis
Results in low platelets from consumption
Most clinically relevant feature of Platelet factor 4
PF4 - (released from alpha granules)
– Is HIT
Serotonin
Stored in dense granules
- released on activation of platelets
Basis for serotonin release assay
Serotonin release assay
Diagnostic test for HIT
Donor platelets radiolabeled with serotonin
patient serum and heparin added to the donor platelets
Presence of HIT antibodies –> cause excessive serotonin release from donor platelets
ADP
Released from dense granules
Also released by RBCs when damaged
Binds to 2 G-Protein receptors found on platelets:
– P2Y1 & P2Y12
Binding leads to decreased cAMP formation
—- High cAMP blocks platelet activation
Which receptors does ADP bind to on platelet?
P2Y1 - causing calcium release and change in platelet shape
P2Y12 - platelet degranulation and increased aggregation
Leading to dec cAMP
Causing activation
Which drugs cause an increase in cAMP in platelets
Phosphodiesterase inhibitors
P2Y12 receptor blocking drugs
ADP receptor blockers
Inhibits platelet activity
Clopidogrel, prasugrel, ticlopidine, ticagrelor
TXA2
Thromboxane A2
Powerful platelet activator
(COX convertes AA to…)
Arachadonic Acid -> TXA2
Aspirin inhibits COX -> decreased TXA2 -> Decreased platelet activation
Test of platelet function
Bleeding time - because superficial bleeding is mostly managed by platelets
