Arterial Thrombosis and Antiplatelet Drugs

Question 1

Describe how atherosclerosis occurs in a vessel?

Answer 1

Not the same as arterial thrombosis

• Damage to endothelium
• Recruit ‘foamy’ macrophages rich in cholesterol
  => Forms plaques rich in cholesterol

Question 2

If an atherosclerotic plaque is stable and has not fully occluded a vessel, what symptoms can become apparent in the patient?

Answer 2

• less O2 blood reaching end organ
  => chest pain on exertion
  => claudication

Question 3

What can happen if an atherosclerotic plaque is unstable and ruptures?

Answer 3

• Plaques rupture
• exposes endothelium and vWF
• platelets aggragate on vessel wall and release granules to attract other platelets to site

Question 4

What risk factors can predispose patients to arterial thrombosis?

Answer 4

• Hypertension (damage to endothelium, platelet activation)
• Smoking (damages endothelium, indirectly increases BP)
• High cholesterol (accumulated in plaque)
• Diabetes mellitus

Question 5

How is arterial thrombosis prevented?

Answer 5

• stop smoking
• Tx hypertension and diabetes
• lower cholesterol
• give antiplatelet drugs

Question 6

How do platelets attach to the collagen exposed on the vessel wall? And how do they attach to each other?

Answer 6

Attach to WALL via:
glycoprotein 1B

Attach to each OTHER via:
glycoprotein IIb/IIIa

Question 7

Why do platelets change their surface shape to expose more phospholipid?

Answer 7

• greater surface area for coagulation activation and fibrin production to stabilise the clot.

Question 8

What granules do the platelets release to attract others to the clot site?

Answer 8

granules stimulate platelet activation:

• Thrombin
• Thromboxane A2
• ADP

Question 9

Describe how aspirin works to decrease the number of platelets attracted to the site of the arterial clot

Answer 9

Inhibits cyclo-oxygenase which is needed to make Thromboxane A2

• thromboxane A2 = granule released to attract other platelets

Question 10

How do drugs such as Clopidogrel and Prasugrel work ?

Answer 10

Clopidogrel, prasugrel
- ADP receptor antagonists
=> attach to ADP receptor and dont let ADP granules attach to send out signal to other platelets

Question 11

How does Dipyridamole work as an antiplatelet drug?

Answer 11

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

Question 12

When should antiplatelet drugs be stopped before an operation?

Answer 12

7 days before
- consult cardiologist if patient has an important cardiac stent that requires them to stay on antiplatelets prior to the procedure

Question 13

What are the potential side effects of aspirin?

Answer 13

1. Bleeding
2. Blocks production of prostaglandins:
   => GI ulceration
   => Bronchospasm (dont give if asthmatic!)

Question 14

What antibody can be given to inhibit platelets sticking together?

Answer 14

Abciximab (given IV)

- inhibits Glycoprotein IIb/IIIa to stop platelets aggregating

Question 15

If a patient undergoes serious bleeding due to an antiplatelet drug how can this be fixed?

Answer 15

• platelet transfusion