Platelets Flashcards
What initiates platelet plug formation?
Damage to endothelium of blood vessels- exposed collagen
What receptors bind to collagen?
GPIb receptors
VWF
What causes platelet activation?
1) Binding platelets to collagen fibres triggers
release contents of secretory vesicles
2) Platelets bind collagen (lead release
Thromboxane A2)
3) Thrombin binds PAR1 (lead release ADP
from dense granules)
What is the effect of platelet activation?
Effects of platelet activation:
1) Change shape- smooth discoid to spiculated and pseudopodia
2) Increased GbIIb/IIIa expression
- form crosslinks other receptors of platelets
by binding to fibrinogen- results in
aggregation
What does ADP bind to? Function
P2Y1 (activation/amplification)
P2Y12 (activation)
What granules do platelets contain?
Electron dense- Ca2+, ADP/ATP, serotonin
Alpha granule- platelet derived growth factor
fibrinogen, vWF
Function thrombin?
1) Activation- thrombin binds PAR1 and PAR4
- activate platelets
- induce further thrombin release- positive
feedback
2) Thrombin plays part in coagulation
cascade- converts fibrinogen into fibrin-
crosslinking
What is ADP released from?
Platelet dense granules
What does ADP act on? What type receptors- function?
2 purinergic receptors:
P2Y1 and P2Y12
P2Y1- Gq coupled receptor
- release phospholipase C beta
- induces calcium mobilisation and
activation platelets
P2Y12- Gi coupled receptor and
- inhibits adenylate cyclase converted
to cyclic AMP
- therefore increased activation platelets
What inhibits activation platelets?
cAMP
What does ATP bind to? function?
P2X1- cause platelet amplification
What does platelet amplification cause?
Increased expression GbIIb/IIIa
Crosslink with GbIIb/IIIa receptors on other platelets by binding to fibrinogen
New platelets bind old ones- this is called platelet aggregation- positive feedback
How are platelets activated?
Thromboxane A2 binds to TPα
- increases platelet aggregation
- stimulates vasoconstriction
What inhibits platelet aggregation and vasoconstriction?
Prostacyclin
Presence COX1 and COX2 convert arachidonic acid into prostaglandin- prostacyclin
What effect does aspirin have?
Inhibit COX1 meaning less thrombaxane A2
- less aggregation/activation
What effect does aspirin have?
Inhibit COX1 meaning less thromboxane A2
- less aggregation/activation
other NSAIDS inhibit COX1 and COX2
- inhibition
issue cardiovascular patients
How is platelet plug formed?
1) Damage BV leads exposure collagen
2) Adhesion platelets to collagen directly
through glycoprotein 1a leads exposure
glycoprotein IIb./IIIa
3) VWF binds collagen through IIb/IIIa
glycoproteins
- increases platelet adhesion
4) Platelet contains 2 types granules:
- electron dense granules
- alpha granules
Electron dense granules release:
ADP/ATP, serotonin and calcium
ADP acts on P2Y1/P2Y12- lead further
activation
ATP binds P2X1
5) Thrombin binds to PAR1 and PAR4-
platelet activation
6) Activation of platelets:
- change shape from discoid to spiculated/
pseudopodia
- increase SA platelet
7) Activation platelets lead increase
expression IIb/IIIa
8) Fibrinogen secreted alpha granules bind to
receptors
- new platelets adhere old ones- platelet
aggregation
9) Platelets produce thromboxane A2
- aid in vasoconstriction
- reduced blood flow aids forming primary
haemostatic plug
10) Thromboxane and serotonin stimulate
vasoconstriction – reduced blood flow
- aid in forming primary haemostatic plug
