Arterial Thrombosis and Anti-Platelet Drugs

Question 1

What will an arterial thrombosis lead to?

Answer 1

MI
Stroke
Critical limb ischaemia

Question 2

Describe an arterial thrombosis?

Answer 2

Failure in primary haemostasis

Platelet rich thrombus

Question 3

What is atherosclerosis?

Answer 3

Damage to endothelium of arteries
Recruitment of foamy macrophages rich in cholesterol
Forms plaques rich in cholesterol

Question 4

What does a stable atherosclerotic plaque look like histologically?

Answer 4

Hyalinised and calcified

Result in stable angina and intermittent claudication

Question 5

What does an unstable atherosclerotic plaque look like?

Answer 5

Plaque rupture
Platelets recruited
Acute thrombosis

Question 6

Why does plaque rupture lead to platelet aggregration?

Answer 6

Platelet adheres to exposed endothelium and release of VWF
Platelets activated; release of granules that activate coagulation and recruit platelets
Platelet aggregation via membrane glycoprotein

Question 7

What are risk factors for arterial thrombosis?

Answer 7

Factors that damage endothelium, increase foamy macrophages and activate platelets 
Hypertension (damage to endothelium, platelet activation) 
Smoking (endothelium, platelets) 
High cholesterol (accumulated in plaque) 
DM (endothelium, platelets, cholesterol)

Question 8

How can arterial thrombosis be prevented?

Answer 8

Stop smoking
Treat hypertx
Treat diabetes
Lower cholesterol
Anti-platelet drugs

Question 9

What leads to platelet adhesion?

Answer 9

Endothelial damage exposing VWF and other proteins to which platelets have receptors

Question 10

What leads to platelet aggregation?

Answer 10

Secretion of ADP and thromboxane A2

Question 11

What receptor present on platelets will bind to VWF?

Answer 11

Glycoprotein 1b

Question 12

What receptor present on platelets will allow them to stick together in platelet adhesion?

Answer 12

Glycoprotein 2b/3a

Question 13

Why will platelets alter their shape once adhesion occurs?

Answer 13

Expose more phospholipid on surface to increased SA for coagulation activation and fibrin production

Question 14

What is the mechanism of aspirin?

Answer 14

Inhibits cyclooxygenase which is necessary to produce thromboxane A2

Question 15

What are the side effects to aspirin?

Answer 15

Bleeding

Due to blockage of prostaglandins; GI ulceration, bronchospasm, renal issues

Question 16

What is the mechanism of clopidogrel and prasugrel?

Answer 16

ADP receptor (P2Y12) antagonists

Question 17

What is the mechanism of dipyridamole?

Answer 17

Phosphodiesterase inhibitor; reduced production of cAMP which is a “second messenger” in platelet activation

Question 18

What is the mechanism of abciximab?

Answer 18

Glycoprotein 2b/3a inhibitors preventing aggregation of platelets
Only really used in cardiac surgery

Question 19

What is the lifespan of a platelets?

Answer 19

7-10 days

Question 20

For how long before surgery should antiplatelets be stopped?

Answer 20

7 days

Question 21

What can be done in the event of serious bleeding due to anti-platelet use?

Answer 21

Platelet transfusion