Week 3- arterial thrombosis and anti-platelet drugs

Question 1

Is atherosclerosis the same as arterial thrombosis?

What is atherosclerosis?

Answer 1

No they are not the same.
Damage to endothelium causes recruitment of macrophages, they eat the cholesterol forming ‘foamy macrophages’
This forms plaques rich in cholesterol.

Question 2

when is an atherosclerotic plaque stable?

Answer 2

When it is hylanised and calcified.

Question 3

In what conditions do you get stable atherosclerotic plaques?

Answer 3

Stable angina

Intermittent claudication

Question 4

What is an unstable atherosclerotic plaque?

What symptoms will be seen?

Answer 4

The plaque ruptures. Platelets are then recruited and cause acute thrombosis.
The symptoms will be sudden onset. They will depend on the area.

Question 5

Give examples of conditions with unstable atherosclerotic plaques?

Answer 5

Unstable angine, MI’s, stroke.

Question 6

What does unstable atherosclerotic plaques eventually lead too?

Answer 6

Organ ischaemia and infarction.

Question 7

Describe the relationship between platelets and arterial thrombus?

Answer 7

The plaque ruptures in the high pressure environment of the arteries. The endothelium is exposed and VWF is exposed, meaning platelets adhere to it. Platelets become activated releasing granules that activate coagulation and recruit other platelets to the developing plug.
Platelet aggregation occurs via membrane glycoproteins.

Question 8

What are some risk factors for arterial thrombosis?

Answer 8

Any factors causing damage to the endothelium, increase in foamy macrophages and platelet activation. 
Hypertension (damage to endothelium, platelets)
Smoking (endothelium, platelets)
High cholesterol (accumulates in the plaque)
Diabetes mellitus (endothelium, platelets, cholesterol)

Question 9

How can you prevent arterial thrombosis?

Answer 9

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

Question 10

How do platelets bind to collagen when they are forming the platelet plug? What is the term for this?

Answer 10

Via VWF and glycoprotein 1b.

Called adhesion

Question 11

What occurs during aggregation of the platelet plug?

Answer 11

Platelets attach to each other via GPIIbIIIa and fibrinogen. At the same time as this activation is occurring.

Question 12

What is activation of platelets?

Answer 12

Platlets alter their shape to expose more phospholipid on the surface- providing a greater surface area for coagulation activation and fibrin clot formation.

Question 13

What augments the activation of platelets?

Answer 13

Augmented by release of granules that further stimulate platelet activation e.g. thrombin, thromboxane A2 and ADP In order to recruit more platelets into the process. This occurs via receptors to ADP on the platelet surface.

Question 14

How does aspirin work?

Answer 14

It inhibits cyclo-oxygenase (COX) which is necessary to produce thromboxane A2 (a platelet agonist released from granules)

Question 15

Side effects of aspirin?

Answer 15

Bleeding
Blocks production of prostaglandins
Gi ulcers
Bronchospasm

Question 16

What other anti platelet drugs exist?

Answer 16

Clopidogrel and prasugrel- they work by being ADP receptor antagonists.
Dypiridamole- phosphodiesterase inhibitor- reduces production of cAMP which is the ‘second messenger’ in platelet activation

Question 17

How do GPIIb/IIIa inhibitors work?

Answer 17

They inhibit aggregation of the platelet plug. e.g. abciximab.

Question 18

When should you stop anti platelet drugs before operations?

Answer 18

7-10 days before as the anti platelet drugs affect platelets for their lifespan (which is 7-10 days).

Question 19

How can you reverse the effects of anti platelet drugs in serious bleeds?

Answer 19

Platelet transfusion.