Arterial thrombosis & anti-platelet drugs

Question 1

Give the 2 cardinal features of arterial thrombosis?

-general management?

Answer 1

atherosclerosis+ platelet rich thrombus
-aspirin & other anti-platelet drugs
+modify risk factors

Question 2

What is atherosclerosis?

Answer 2

the formation of a cholesterol rich plaque on vessel walls, causing damage to the endothelium

Question 3

describe a stable atherosclerotic plaque?

-examples of pathology?

Answer 3

Hyalinised and calcified

-e.g. in stable angina and intermittent claudication

Question 4

Describe and unstable atherosclerotic plaque?

-examples of pathology?

Answer 4

plaques rupture, platelets are recruited and cause acute thrombosis

-Sudden onset of symptoms
e.g. unstable angina /MI
Stroke

Question 5

Describe how an arterial thrombosis occurs?

Answer 5

Plaque rupture is more likely in the high pressure environment of the arteries

• The endothelium is exposed and vWF is released meaning platelets adhere
• Platelets become activated and release granules that activate coagulation and recruit other platelets to develop platelet plug
• platelet aggregation occurs via membrane glycoproteins

Question 6

Risk factors for arterial thrombosis? (4)

-give the 5 areas of preventing arterial thrombosis?

Answer 6

Hypertension 
(causes damage to the endothelium and platelet activation)
Smoking
(damage endothelium, platelets)
High cholesterol 
(plaque accumulation)
DM
(endothelium, platelets, cholesterol) 
*ALL DAMAGE ENDOTHELIUM*

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

Question 7

Platelets

• where are platelets formed?
• describe their structure?
• how does platelet adhesion occur?
• how does platelets aggregation occur?
• what is platelet activation?
• what process do antiplatelet drugs target?

Answer 7

Formed in the bone marrow by budding from megakaryocytes

• small nucleated discs
• endothelial damage exposes collagen and VWF and other proteins to which platelets have receptors- get platelet adhesion at the site of injury via binding with glycoprotein 1B and VWF
• secretion of chemicals from the platelets (ADP, thromboxane 2) leads to aggregation, platelets attach to each other via glycoprotein 2B3A and fibrinogen

-when platelets alter their shape to expose more phospholipid on the surface, providing greater SA for coagulation, activation and fibrin production to stabilise the clot
further augmented by granules containing Thrombin, thromboxane A2 and ADP
receptors to ADP on platelet surface

-platelet aggregation

Question 8

Aspirin

• mode of action?
• SE? (2)

Answer 8

inhibits cyclo-oxygenase necessary to produce thromboxane A2

-Bleeding
blocks production of prostaglandins
GI ulceration
Bronchospasm

Question 9

Clopidogrel, Prasugrel

-mode of action?

Answer 9

ADP receptor antagonist so prevents platelet aggregation

Question 10

Dipyridamole

• mode of action?
• adv?
• disadv?

Answer 10

phosphodiesterase inhibitor- reduces production of cAMP which is a ‘second messenger’ in platelets activation

• no prostaglandin inhibition
• higher risk of bleeding

Question 11

Abciximab

-mode of action?

Answer 11

-GP 2B/3A inhibitors i.e. inhibit aggregation

given IV

Question 12

bleeding on anti platelets

• period of action?
• reversal?

Answer 12

• need to stop anti platelet 7-10 days prior to surgery

- serious bleeding- reverse with platelet transfusion

Question 13

Comparing arterial and venous thrombosis:

• underlying cause?
• type of clot?
• preventative drugs?

Answer 13

-Arterial
inflammatory disorder instigated by damage to endothelium
Venous
low pressure system, mainly due to stasis

-Arterial 
platelets central and recruited to ruptured plaques
Venous 
Platelets not largely involved and clots are fibrin rich  
-Arterial 
antiplatelet drugs 
Venous 
anticoagulant drugs