3.6 Arterial thrombosis and anti-platelet drugs

Question 1

stable atherosclerotic plaques characteristics

Answer 1

hyalinised
calcified
stable angina, intermittent claudication

Question 2

unstable atherosclerotic plaques

Answer 2

plaques rupture, platelets recruited, cause acute thrombosis
sudden onset of symptoms
unstable angina or MI, stroke - acute organ ischaemia and infarction

Question 3

what is the sequence of events in arterial thrombosis?

Answer 3

plaque rupture in high pressure environment
platelets adhere
exposed endothemlium binds von willebrand and platelet
activation of platelets- granules that activate coagulation and develop platelet plug
membrane glycoproteins cause platelet aggrestion - surface glycoprotein 1b (surfaces), and IIb/IIIa- stick to each other

Question 4

RF that damage endothelium, increase foamy macrophage and platelet activation

Answer 4

HTN
smoking
high cholesterol
diabetes

reduce the risk by reducing these, and giving anti-platelet drug

Question 5

what chemicals do platelets secrete that lead to aggregation of platelets?

Answer 5

ADP
thromboxane A2
thrombin

Question 6

what do platelets bind on exposed endothelium?

Answer 6

subendothelial collagen is adhered to by:

• glycoprotein 1b
• von willebrand factor

Question 7

what do platelets use to bind each other and fibrinogen?

Answer 7

GP IIb

GP IIIa

Question 8

what is the effect of protein shape changing in activation?

Answer 8

expose more phospholipid

Question 9

what role does aspirin play in arterial thrombosis?

Answer 9

aspirin inhibits COX, enzyme that eventually produces thromboxane A2
-platelet agonist released from platelet granules on activation

actually COX inhibition prevents arachadonic acid from turning into prostaglandin G2/H2
a second enzyme- thromboxane synthase actually turns prostagland in G2/H2 –> thromboxane A2 which causes platelet activation and aggregation

Question 10

side effects of aspirin

Answer 10

bleeding
blocks prostaglandins- GI ulceration, bronchospasm
contraindicated in asthma

Question 11

what is the mechanism for clopidogrel and prasugrel?

Answer 11

ADP receptor antagonists
clopidogrel is more effective
reduced incidence of peptic ulceration

Question 12

what is the mechanism of dipyridamole?

Answer 12

phosphodisterase inhibitor

-reduced cAMMP that is a second messenger in platelet activation

Question 13

abcixamab - what is it, what does it do?

Answer 13

abciximab is a GP IIb/IIIa inhibitor, and it prevents platelet aggregation
used in cardiac surgery, angioplasty, potent.

Question 14

what should be done to antiplatelet drugs prior to surgery?

Answer 14

stop antiplatelet agents 7 days prior to elective operations
-antiplatelet drugs tend to affect platelet function for their 7-10 day lifespan

if there is serious bleeding- reverse with platelet transfusion