Arterial Thrombosis and Anti-Platelet Drugs

Question 1

What are some thrombotic events?

Answer 1

Arterial- coronary, cerebral, peripheral

Venous- DVT, PE

Question 2

Describe atherosclerosis

Answer 2

Not the same as arterial thrombosis
Damage to endothelium
Recruitment of ‘foamy’ macrophages rich in cholesterol
Forms plaques rich in cholesterol

Question 3

Describe stable atherosclerotic plaques

Answer 3

Hyalinsed and calcified

Stable plaques: stable angina (coronary artery), intermittent claudication

Question 4

Describe unstable atherosclerotic plaques

Answer 4

Plaques rupture, platelets are recruited and cause acute thrombosis
Sudden onset of symptoms
Unstable angina or myocardial infarction (coronary arteries)
Stroke (cerebral arteries)

Question 5

Describe platelet adhesion and aggregation in plaque rupture

Answer 5

Rupture- more likely in the high pressure environment of arteries
Platelet adheres to it – exposed endothelium and release of Von Willebrand factor
Platelets becomes activated - release granules that activate coagulation and recruit other platelets to developing platelet plug
Platelet aggregation via membrane glycoproteins

Question 6

What are RFs for arterial thrombosis?

Answer 6

Factors that cause damage to endothelium, increase in foamy macrophages and platelet activation:
Hypertension (damage to endothelium, platelet activation)
Smoking (endothelium, platelets)
High cholesterol (accumulated in plaque)
Diabetes mellitus (endothelium, platelets, cholesterol)

Question 7

How can arterial thrombosis be prevented?

Answer 7

Stop smoking
Treat HT
Treat DM
Lower cholesterol
Anti-platelet drugs

Question 8

Secretion of what chemicals from platelets lead to aggregation of platelets at the site of injury?

Answer 8

ADP

Thromboxane A2

Question 9

In adhesion what do platelets bind to subendothelial collagen via?

Answer 9

Glycoprotein 1b and vWF

Question 10

In aggregation what do platelets attach to each other via?

Answer 10

GP IIb/IIIa and fibrinogen

Question 11

What occurs in platelet activation?

Answer 11

Alter shape to expose more phospholipid on the surface- provides greater SA for coagulation activation and fibrin production to stabilise clot
Process augmented by release of granules that further stimulate activation (e.g. Thrombin, Thromboxane A2, ADP) in order to recruit more platelets to process
Occurs via receptors to ADP etc on platelet surface

Question 12

What is the MOA of Aspirin?

Answer 12

Inhibits cyclo-oxygenase which is necessary to produce Thromboxane A2 (a platelet agonist released from granules on activation)

Question 13

What are the side effects of aspirin?

Answer 13

Bleeding

Blocks production of prostaglandins: GI ulceration, Bronchospasm

Question 14

What is the MOA of clopidogrel/prasugrel?

Answer 14

ADP receptor antagonist

Question 15

What is the MOA of dipyridamole?

Answer 15

Phosphodiesterase inhibitor -reduces production of cAMP which is a ‘second messenger’ in platelet activation

Question 16

What do GP IIb/IIIa inhibitors do?

Answer 16

Inhibit aggregation

Eg abciximab

Question 17

When should anti-platelet agents be stopped prior to elective operations?

Answer 17

7 days (drugs tend to affect function for their 7-10 day life span)

Question 18

How can serious bleeding be reserved if on anti-platelet drugs?

Answer 18

Platelet transfusion