Arterial thrombosis and anti-platelets Flashcards
What are the 3 main types of arterial thrombotic events ?
Coronary, cerebral, peripheral (PVD)
Note however if a cerebral (stroke) is linked to be due to AF then it will be a fibrin dependent clot and the long-term management includes anti-coagulants not anti-platelets
What type of clot forms in arterial thrombosis ?
Platelet rich
What is the main pathogenesis mechanism behind arterial thrombosis formation ?
atherosclerosis formation
Describe the formation of atherosclerosis
- Damage to endothelium (vessel wall) occurs
- Recruitment of ‘foamy’ macrophages rich in cholesterol
- Forms plaques rich in cholesterol
They’re made of cholesterol, fatty substances, cellular waste products, calcium and fibrin (a clotting material in the blood).
What conditions do stable atherosclerotic plaques result in ?
- Stable angina (coronary artery)
- Intermittent claudication (leg artery)
Pic shows an atherosclerotic plaque
What happens in unstable artherosclerotic plaques ?
- Plaques rupture, platelets are recruited and cause acute thrombosis
- This results in sudden onset of symptoms
What conditions are associated with unstable atherosclerotic plaques ?
- Unstable angina or myocardial infarction (coronary arteries)
- Stroke (cerebral arteries)
How does thrombosis (platelet rich) occur when a atherosclerotic plaque ruptures ?
- The arteries are high pressure environments and can ==> cause the plaques to rupture (think this is why you don’t get this in venous system because its a low pressure system so wont rupture any plaques forming in it)
- lPlatelet adheres to it – due to exposed endothelium (collagen) and release of VWF
- lPlatelets becomes activated - release granules that activate coagulation and recruit other platelets to developing platelet plug
- Platelet aggregation via membrane glycoproteins
(basically the steps for primary haemostasis)
What are the risk factors for arterial thrombosis ?
Risk factors are those which cause damage to the endothelium, increase in foamy macrophages and platelet activation
- Hypertension (damage to endothelium, platelet activation)
- Smoking (endothelium, platelets)
- High cholesterol (accumulated in plaque)
- Diabetes mellitus (endothelium, platelets, cholesterol)
What are the prevention treatments for reducing the chances of arterial thrombosis ?
- Stop smoking
- Treat hypertension
- Treat diabetes
- Lower cholesterol – statins
- Anti-platelet drugs
The arterial system is a high pressure environment with a thick smooth muscle layer in the vessel walls ?
T or F
True
Recall that the vessel damage which predisposes to venous thrombosis is not atheroma formation but mainly valve damage in the veins
What are the 4 main types of anti-platelet drugs ?
- Aspirin
- ADP receptor antagonist - e.g. Clopidogrel, prasugrel
- Dipyridamole
- GP IIb/IIIa inhibitors - e.g. abciximab
Describe the action of aspirin
Inhibits cyclo-oxygenase which is necessary to produce Thromboxane A2
What are the potential side effects of aspirin ?
- Bleeding
- Blocks production of prostaglandins:
- GI ulceration
- Bronchospasm
What are the contra-indications to aspirin use ?
Contraindications:
- Recent or current ulcer or gastrointestinal bleeding
- Bleeding disorders e.g. haemophilia
Caution with use:
- Allergy to aspirin, products containing aspirin, or aspirin-like products e.g. ibuprofen or naproxen
- Asthma - can cause bronchospasm want to avoid this in these patients
What is the mechanism of action of Clopidogrel and prasugrel ?
ADP receptor antagonists - prevents platelet activation/recruitment
What is the mechanism of action of Dipyridamole?
Phosphodiesterase inhibitor -reduces production of cAMP which is a ‘second messenger’ in platelet activation
What is the mechanism of action of abciximab?
It is a GP IIb/IIIa inhibitor - this prevents platelet aggregation as this is one of the 2 components that platelets attach to each other by
What is the main adverse effect which can occur due to anti-platelet therapy ?
Bleeding
Why is it important to know the lifespan of platelets ?
The lifepsan is 7-10 days and its important to know this because anti-platelets should be stopped 7 days prior to elective operations
If a patient presents with serious (life-threatening) bleeding how is anti-platelet therapy reversed ?
Platelet transfusion
What is the treatment of atheroembolic ischaemic strokes ?
If presents within 4.5hrs of onset of symptoms give altepase, if presents after 4.5hrs of onset then give aspirin
Continue aspirin therapy for 2wks
For atheroembolic give clopidogrel + statin + anti-HTN treatment
What is the treatment for myocardial infarctions ?
MONA + C - morphine, oxygen, GTN, asprin + prasugrel or ticagrelor (as alternatives to clopidogrel as more effective and okay to use if no history of stroke/TIA and <75)
PCI if presentation is within 12 hours of onset of symptoms and primary PCI can be delivered within 120 minutes of the time when fibrinolysis could have been given.
Offer fibrinolysis to people with acute STEMI presenting within 12 hours of onset of symptoms if primary PCI cannot be delivered within 120 minutes of the time when fibrinolysis could have been given.
Prevention following MI:
SABA + C
Statin, Aspirin, Beta-blocker, ACEi + (clopidogrel, prasugrel or ticagrelor)
What is peripheral arterial disease ?
Peripheral arterial disease (PAD) includes a range of arterial syndromes that are caused by atherosclerotic obstruction of the lower-extremity arteries.
Many people with PAD have no symptoms. However, some develop a painful ache in their legs when they walk, which usually disappears after a few minutes’ rest. The medical term for this is “intermittent claudication”.
What are the main types of peripheral arterial disease ?
exercise and risk factor modification
Anti-platlet therapy:
- 1st line = clopidogrel
- 2nd line = aspirin
