Platelet activation - Haemostasis - BB

Question 1

Which hormone regulates the production of platelets:

Answer 1

TPO - thrombopoietin

Glycoprotein produced mostly in the liver

Question 2

Mechanisms of activating platelets:

Answer 2

1. endothelial injury (direct)

2. stimuli from other activated platelets (indirect)

Question 2

Mechanisms of activating platelets:

Answer 2

1. endothelial injury (direct)

2. stimuli from other activated platelets (indirect)

Question 3

Where is vWF synthesised and storred?

Answer 3

synthesised by endothelial cells and megakaryocytes

Stored in:
- Weibel-Palade bodies in endothelial cells
- Alpha granules in platelets
some found in the plasma

Question 4

vWF release:

Answer 4

From alpha-granules - when platelets are activated

From weibel-palade bodies - when endothelial cells are damaged

Question 5

Roles of vWF (x3)

Answer 5

1. Carrier protein for VIII - [released in presence of thrombin]
2. Binds platelets to damaged endothelium (adhesion)
3. Binds activated platelets together (aggregations)

Question 6

Platelet adhesion (1/3)

Answer 6

Vascular damage - leads to exposure of collagen

Subendothelial collagen binds to vWF

vWF binds to GP1b receptor on platelets

Question 7

Platelet aggregation: (2/3)

Answer 7

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

Question 8

Intermediates for platelet aggregation

Answer 8

GPIIb/IIIa can bind either fibrinogen or vWF

Question 9

Platelet secretion: (3/3)

Answer 9

Platelets are activated either by:

• binding to subendothelial collagen
• stimulation by activating substances (released from other platelets)

2 types of granules - Alpha and dense

Question 10

Contents of platelet alpha granules:

Answer 10

(most abundant)
Fibrinogen
vWF
Platelet factor 4

Question 11

Contents of platelet Dense granules

Answer 11

ADP - activates other platelets
Calcium - for coag cascade
Serotonin

Question 12

HIT

Answer 12

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

Question 13

Most clinically relevant feature of Platelet factor 4

Answer 13

PF4 - (released from alpha granules)

– Is HIT

Question 14

Serotonin

Answer 14

Stored in dense granules
- released on activation of platelets

Basis for serotonin release assay

Question 15

Serotonin release assay

Answer 15

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

Question 16

ADP

Answer 16

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

Question 17

Which receptors does ADP bind to on platelet?

Answer 17

P2Y1 - causing calcium release and change in platelet shape

P2Y12 - platelet degranulation and increased aggregation

Leading to dec cAMP
Causing activation

Question 18

Which drugs cause an increase in cAMP in platelets

Answer 18

Phosphodiesterase inhibitors

Question 19

P2Y12 receptor blocking drugs

Answer 19

ADP receptor blockers

Inhibits platelet activity

Clopidogrel, prasugrel, ticlopidine, ticagrelor

Question 20

TXA2

Answer 20

Thromboxane A2

Powerful platelet activator

(COX convertes AA to…)
Arachadonic Acid -> TXA2

Aspirin inhibits COX -> decreased TXA2 -> Decreased platelet activation

Question 21

Test of platelet function

Answer 21

Bleeding time - because superficial bleeding is mostly managed by platelets