HS5 - Arterial Thrombosis

Question 1

What is thrombosis?

Answer 1

• Too much platelet activity or excessive coagulation

Question 2

Arterial thrombosis occurs when which form of haemostasis has gone wrong?

Answer 2

• Primary haemostasis

Question 3

Venous thrombosis occurs when which form of haemostasis has gone wrong

Answer 3

• Secondary haemostasis

Question 4

Where does arterial thrombosis tend to occur?

Answer 4

• At the site of an atheroma

Question 5

What is an atheroma?

Answer 5

• A buildup of fatty deposits with a fibrous cap In the wall of a blood vessel.

Question 6

When a calcified plaque ruptures why does this course a thrombosis to occur?

Answer 6

• Blood is exposed to procoagulant and platelet activating substances such as collagen.

Question 7

What sort of cells do you find in atherosclerotic plaques?

Answer 7

• Foam cells

Question 8

How are foam cells formed?

Answer 8

• Monocytes migrate to plaque
• become macrophages
• become engorged on fatty material
and then die

Question 9

When a plaque ruptures blood is exposed to tissue factor this causes the conversion of prothrombin to what?

Answer 9

• Thrombin

Question 10

When a plaque ruptures the exposure of blood to tissue factor and collagen results in the formation of what at the site of the ruptured plaque?

Answer 10

• Platelet plug

Question 11

Drug treatment strategies for treating arterial thrombosis relies on trying to stop platelets aggregating by targeting 3 things what are they?

Answer 11

• Inhibition of platelets
• inhibition of fibrin formation
• augmentation of fibrinolysis

Question 12

Name 5 types of antithrombotic drugs used to treat arterial thrombosis.

Answer 12

• Aspirin
• heparin
• ADP receptor antagonists (clopidogrel, prasugrel)
• platelet GPIIb/IIIa inhibitors (ReoPro, tirofiban)
• thrombolytics (streptokinase, tPA)

Question 13

3 types of surgical interventions are used to treat arterial thrombosis, name these.

Answer 13

• Balloon angioplasty (PTCA)
• stenting
• CABG (coronary artery bypass grafts)

Question 14

What are the side-effects of aspirin?

Answer 14

• Dyspepsia
• heartburn
• GI bleeding
• allergy

Question 15

Name 2 types of second-generation platelet inhibitors.

Answer 15

• Clopidogrel

* GPIIb/IIIa inhibitors

Question 16

Clopidogrel is a second-generation platelet inhibitor, what does it target?

Answer 16

• P2Y12 ADP Receptor

Question 17

Clopidogrel is an irreversible antagonist of what?

Answer 17

• P2Y12 ADP Receptor

Question 18

What is the effect of clopidogrel on platelets?

Answer 18

• It blocks the effect of ADP on platelets

Question 19

clopidogrel is a pro-drug so what needs to happen to it before it becomes active?

Answer 19

• Metabolised in the liver

Question 20

What do GPIIb/IIIa inhibitors do?

Answer 20

• Stop fibrinogen binding to platelet receptors

Question 21

GPIIb/IIIa stop fibrinogen binding to platelet receptors so they completely block what?

Answer 21

• Aggregation

Question 22

What is one problem with clopidogrel?

Answer 22

• Liver metabolism, rates of metabolism varies between individuals - some people don’t respond.

Question 23

Ticagrelor is a third-generation platelet inhibitor with 3 main benefits what are these?

Answer 23

• No need for prodrug metabolism
• reversible antagonist
• orally active

Question 24

What type of enzyme is thrombin?

Answer 24

• Protease

Question 25

How does thrombin activate platelets?

Answer 25

• Chops terminal NH2 off protease activating receptor-1 (PAR-1) on the surface of platelets.
• residual tethered ligand folds back and binds to a different part of the receptor
• auto activates the receptor