Arterial Thrombosis and Anti-Platelet Drugs Flashcards
What will an arterial thrombosis lead to?
MI
Stroke
Critical limb ischaemia
Describe an arterial thrombosis?
Failure in primary haemostasis
Platelet rich thrombus
What is atherosclerosis?
Damage to endothelium of arteries
Recruitment of foamy macrophages rich in cholesterol
Forms plaques rich in cholesterol
What does a stable atherosclerotic plaque look like histologically?
Hyalinised and calcified
Result in stable angina and intermittent claudication
What does an unstable atherosclerotic plaque look like?
Plaque rupture
Platelets recruited
Acute thrombosis
Why does plaque rupture lead to platelet aggregration?
Platelet adheres to exposed endothelium and release of VWF
Platelets activated; release of granules that activate coagulation and recruit platelets
Platelet aggregation via membrane glycoprotein
What are risk factors for arterial thrombosis?
Factors that damage endothelium, increase foamy macrophages and activate platelets Hypertension (damage to endothelium, platelet activation) Smoking (endothelium, platelets) High cholesterol (accumulated in plaque) DM (endothelium, platelets, cholesterol)
How can arterial thrombosis be prevented?
Stop smoking Treat hypertx Treat diabetes Lower cholesterol Anti-platelet drugs
What leads to platelet adhesion?
Endothelial damage exposing VWF and other proteins to which platelets have receptors
What leads to platelet aggregation?
Secretion of ADP and thromboxane A2
What receptor present on platelets will bind to VWF?
Glycoprotein 1b
What receptor present on platelets will allow them to stick together in platelet adhesion?
Glycoprotein 2b/3a
Why will platelets alter their shape once adhesion occurs?
Expose more phospholipid on surface to increased SA for coagulation activation and fibrin production
What is the mechanism of aspirin?
Inhibits cyclooxygenase which is necessary to produce thromboxane A2
What are the side effects to aspirin?
Bleeding
Due to blockage of prostaglandins; GI ulceration, bronchospasm, renal issues
What is the mechanism of clopidogrel and prasugrel?
ADP receptor (P2Y12) antagonists
What is the mechanism of dipyridamole?
Phosphodiesterase inhibitor; reduced production of cAMP which is a “second messenger” in platelet activation
What is the mechanism of abciximab?
Glycoprotein 2b/3a inhibitors preventing aggregation of platelets
Only really used in cardiac surgery
What is the lifespan of a platelets?
7-10 days
For how long before surgery should antiplatelets be stopped?
7 days
What can be done in the event of serious bleeding due to anti-platelet use?
Platelet transfusion
