Arterial Thrombosis and Anti-Platelet Drugs

Question 1

What cells are key to arterial thrombosis?

Answer 1

Platelets

Question 2

What causes atherosclerosis?

Answer 2

Macrophages and cholesterol are pushed into vessel wall = may rupture and attract platelets

Question 3

What is the first step in atherosclerosis?

Answer 3

Damage to endothelium

Question 4

Why are atherosclerotic plaques rich in cholesterol?

Answer 4

Foamy macrophages rich in cholesterol are recruited when there is endothelial damage

Question 5

What are the features of stable plaques?

Answer 5

Hyalinised and calcified

Can cause stable angina and intermittent claudication

Question 6

What are the features of unstable plaque?

Answer 6

May rupture and recruit platelets to cause an acute thrombosis = cause acute organ ischaemia/infarction
Sudden onset of symptoms
Cause unstable angina, MI or stroke

Question 7

Why are plaque ruptures more likely in arteries?

Answer 7

Due to the high pressure environment

Question 8

What are the steps of arterial thrombosis formation?

Answer 8

Platelet adherence, activation and aggregation

Question 9

What causes platelets to adhere to plaque ruptures?

Answer 9

Exposed collagen and vWF

Question 10

What occurs when platelets are activated?

Answer 10

Release granules that activate coagulation and recruit other platelets to the developing plug

Question 11

What causes platelet aggregation?

Answer 11

Occurs via membrane glycoproteins

Question 12

What are the risk factors for arterial thrombosis?

Answer 12

Endothelial damage, increase in foamy macrophages and platelet activation

Question 13

What are some conditions that increase the risk of arterial thrombosis?

Answer 13

Hypertension, smoking, high cholesterol, diabetes

Question 14

What are some preventions against arterial thrombosis?

Answer 14

Stop smoking, treat hypertension and diabetes, lower cholesterol, anti-platelets

Question 15

What do platelets bind to in order to stick to exposed subendothelial collagen?

Answer 15

Glycoproteins Ib and vWF

Question 16

What receptors allow platelets to bind to each other?

Answer 16

GP IIb/IIIa and fibrinogen

Question 17

What is the first step in platelet activation?

Answer 17

Platelets alter their shape to expose more phospholipid on their surface

Question 18

What effect do platelets changing their shape have?

Answer 18

Provides greater surface area for coagulation and fibrin production to stabilise the clot

Question 19

What augments the process of platelet activation?

Answer 19

Release of granules which further stimulates activation = thrombin, thromboxane A2, ADP

Question 20

What is the action of aspirin?

Answer 20

Inhibits COX which is necessary to produce thromboxane A2

Question 21

What is the action of thromboxane A2?

Answer 21

Acts as platelet agonist = released from granules on activation

Question 22

What are the side effects of aspirin?

Answer 22

Bleeding, blocks prostaglandin production, GI ulceration, bronchospasm

Question 23

What is the action of clopidogrel?

Answer 23

ADP receptor antagonist

Question 24

What is the action of dipyridamole?

Answer 24

Phosphodiesterase inhibitor which reduces cAMP production = less commonly used

Question 25

What is the action of abciximab?

Answer 25

Inhibits aggregation by blocking GP IIa/IIIb = given via IV

Question 26

For how long do anti-platelets affect platelets?

Answer 26

For their entire lifespan

Question 27

How should bleeding on anti-platelets be managed?

Answer 27

Stop anti-platelet 7 days before elective surgery

Use platelet transfusion if serious bleed