Arterial thrombosis and anti-platelet drugs

Question 1

describe the pathophysiology of atherosclerosis

Answer 1

damage to endothelium causes recruitment of foamy macrophages rich in cholesterol = plaques

Question 2

What is the difference between a stable and unstable plaque

Answer 2

Stable plaque:
-hyalinised and calcified = stable angina and intermittent claudication

Unstable plaque:
-plaques rupture recruiting platelets causing arterial thrombosis = sudden onset symptoms (unstable angina/MI)

Question 3

Describe the 3 different steps in the formation of a platelet plug

Answer 3

1: adhesion - platelets bind to subepithelial collagen via GP1B (glycoprotein) and vWF = causes both aggregation and activation
2: aggregation - platelets attach to eachother via GPIIbIIIa and fibrinogen
3: activation - platelets alter their shape to expose more phospholipid on surface = greater surface area for coagulation activation and fibrin production to stabilise clot. (They release granules to further stimulate platelet activation, activate coagulation and recruit other platelets to site.)

Question 4

List 4 risk factors for arterial thrombosis

Answer 4

• Hypertension (damage to endothelium/platelet activation)
• smoking (endothelium/platelet activation)
• high cholesterol (accumalated in plaque)
• D.M (endothelium/platelets/cholesterol)

Question 5

What are the 4 different antiplatelet drugs?

Answer 5

• Aspirin
• Clopidogrel
• Dypyridamole
• GPIIbIIIa inhibitors

Question 6

Aspirin:

• how does this work
• s/e

Answer 6

-inhibits cyclo-oxygenase = prevents platelet activation and aggregation
(also blocks prostoglandin synthesis which protects stomach mucosa and are involved in bronchodilation)

S/E: bleeding, peptic ulcers, bronchospasm (not for asthmatics)

Question 7

How does clopidogrel work?

Answer 7

ADP receptor antagonist: prevents platelet activation/aggregation

Question 8

How does dipyridamole work?

Answer 8

phosphodiesterase inhibitor - reduces the production of cAMP which = a second messenger in platelet activation

Question 9

GPIIbIIIa inhibitors: how do these work and what is an example?

Answer 9

• Abcliximab
• monoclonal abody binds to GPIIbIIIa and inhibits it = prevent aggregation
• infusion rarely used (only in surgery)

Question 10

Antiplatelets and surgery - when should antiplatelets be stopped prior to surgery?

Answer 10

• antiplatelet drugs affect platelets over their 7-10day lifespan
• stop antiplatelet agents 7 days prior to elective operation
• if serious bleeding - reverse with platelet transfusion