Arterial Thrombosis and Anti-platelet Drugs

Question 1

what are antiplatelets used for?

Answer 1

arterial atherosclerotic events causing a platelet rich thrombus due to rupture

Question 2

arterial thrombosis vs atherosclerosis?

Answer 2

atherosclerosis = the plaque

thrombosis occurs after the plaque ruptures and platelets aggregate at the site forming a thrombus

Question 3

how does atherosclerosis form?

Answer 3

damage to endothelium > recruitment of foamy macrophages rich in cholesterol > cholesterol rich plaque forms

Question 4

describe stable atherosclerotic plaques

Answer 4

hyalinised and calcified

Question 5

what do stable atherosclerotic plaques cause?

Answer 5

stable angina (coronary artery)
intermittent claudication (leg artery)

Question 6

what does unstable atherosclerotic plaque cause?

Answer 6

plaque rupture > recruitment of platelets and acute thrombosis
can cause unstable angina and MI with sudden onset of symptoms
can cause stroke
(generally organ ischaemia and infarction)

Question 7

how is hypertension involved in atherosclerosis?

Answer 7

can cause the initial injury inducing formation of the plaque
high pressure system also makes the plaque more likely to rupture

Question 8

how does an acute thrombosis form?

Answer 8

platelet adheres to exposed endothelium and release of vWF
platelets become activated and release granules that activate coagulation and recruit other platelets to developing platelet plug
platelet aggregation via membrane glycoproteins

Question 9

risk factors for arterial thrombosis?

Answer 9

factors which cause damage to endothelium, increase in foamy macrophages or platelet activation

• hypertension
• smoking
• high cholesterol
• diabetes mellitus

Question 10

how can arterial thrombosis be prevented?

Answer 10

stop smoking
treat hypertension
treat diabetes
lower cholesterol
anti-platelet drugs

Question 11

how are platelets formed?

Answer 11

budding off from cytoplasm of megakaryocytes in bone marrow

Question 12

structure of platelet?

Answer 12

no nucleus
disc shaped
have receptors for vWF and other proteins exposed at site of ruptured plaque
secrete various chemicals which lead to aggregation of platelets

Question 13

what chemicals to platelets secrete?

Answer 13

ADP

thromboxane A2

Question 14

lifespan of platelets?

Answer 14

7-10 days

Question 15

describe platelet adhesion

Answer 15

platelets bind to exposed subendothelial collagen via glycoprotein 1b and vWF

Question 16

describe platelet aggregation

Answer 16

platelets attach to each other via glycoprotein 2b and 3a and fibrinogen

Question 17

what happens at the same time as aggregation?

Answer 17

activation

Question 18

describe platelet activation

Answer 18

platelets alter their shape to expose more phospholipid on the surface which gives a bigger surface area for coagulation activation and fibrin production to stabilise clot
process is augmented by release of granules that further stimulate platelet activation in order to recruit more platelets to the process (occurs via receptors to ADP etc on the platelet surface)

Question 19

how does aspirin work?

Answer 19

inhibits cyclo-oxygenase which is necessary to produce thromboxane A2

Question 20

side effects of aspirin?

Answer 20

bleeding
also blocks production of prostaglandins in the stomach which protects against gastric HCl therefore the stomach isn’t protected and ulceration can occur
can also cause bronchospasm

Question 21

how do clopidogrel and prasugrel work?

Answer 21

ADP receptor antagonists

Question 22

how does dipyridamole work?

Answer 22

phosphodiesterase inhibitor

reduces production of cAMP which is a second messenger in platelet activation

Question 23

which antiplatelet drug inhibit glycoprotein 2b and 3a?

Answer 23

abciximab

- inhibits aggregation of platelets

Question 24

how can bleeding risk be managed with antiplatelets?

Answer 24

anti platelets affect platelet function for their 7-10 day lifespan
should therefore be stopped 7 days prior to elective operations
action can be reversed with platelet transfusion if serious bleeding occurs

Question 25

which is inflammatory, arterial or venous thrombosis?

Answer 25

arterial

Question 26

which causes organ ischaemia?

Answer 26

arterial