Arterial Thrombus and Antiplatelet Drugs Flashcards
What are the 2 main types of thrombotic event?
- Arterial: conorary, cerebral, peripheral
2. Venous: DVT, PE
What type of drug is used to treat an arterial thrombus?
Antiplatelet
What type of drug is used to treat a venous thrombus?
Anticoagulant
Arterial thrombus are found in a ____ pressure system
HIGH
How do arterial thrombus form?
- Atherosclerosis narrows the blood vessel
- This damages the vessel wall
- vWF recruits platelets
- Platelets come and aggregate
- PLATELET RICH THROMBUS is formed
How is an arterial thrombus treated?
- Aspirin and other anti-platelet drugs (e.g. clopidogrel).
* Modify risk factors for atherosclerosis.
What is atherosclerosis not the same as?
Arterial thrombus
Describe how atherosclerosis forms.
- Damage to endothelium.
- Recruitment of ‘foamy’ macrophages rich in cholesterol.
- Forms plaques rich in cholesterol.
Describe stable atherosclerotic plaques.
Hyalinised and calcified
What are the 2 clinical conditions that people get from having a stable atherosclerotic plaque?
- Stable angina (coronary artery).
* Intermittent claudication (leg artery).
How does an unstable atherosclerotic plaque cause an acute thrombus?
Plaques rupture, damage to endothelium, platelets are recruited and cause acute thrombosis
What symptoms arise from an acute thrombus?
Sudden onset sx:
- Unstable angina or myocardial infarction (coronary arteries).
- Stroke (cerebral arteries).
What can an acute thrombus ultimately lead to?
** LEADS TO ACUTE ORGAN ISCHAEMIA AND INFARCTION **
In what type of environment is the rupture of a plaque more likely to happen?
In the high pressure environment of arteries.
Outline how an arterial thrombus develops after the rupture of a plaque?
- Platelets adhere to the ruptured plaque – exposed endothelium and release of Von Willebrand factor.
- Platelets become activated – release granules that activate coagulation and recruit other platelets to developing platelet plug.
- Platelet aggregation via membrane glycoproteins.
What do all the risk factors for an arterial thrombus ultimately do?
Cause damage to the endothelium, increase in foamy macrophages and platelet activation.
List risk factors for arterial thrombus (and state what they effect).
- Hypertension – damage to endothelium, platelet activation.
- Smoking – endothelium, platelets.
- High cholesterol (accumulated in plaque).
- Diabetes mellitus (endothelium, platelets, cholesterol).
How can an arterial thrombus be prevented?
- Stop smoking.
- Treat hypertension.
- Treat diabetes.
- Lower cholesterol.
- Anti-platelet drugs.
The venous system is a ____ pressure system
LOW
What triad is important in understanding the aetiology of a venous thrombus?
Virchow’s triad:
- Stasis.
- Vessel wall (valves not atheroma).
- Hypercoagulability (high clotting factors).
The clot in a venous thrombus is ______ rich
FIBRIN
How is a venous thrombus treated?
- Heparin
- Warfarin
- NOAC’s
Where are platelets formed? How?
In the bone marrow, by ‘budding’ from megakaryocytes.
Describe the appearance of platelets.
Small anucleate discs
What is the lifespan of a platelet?
7-10 days
Explain the steps which lead to PLATELET ADHESION at the site of injury.
Endothelial (vessel wall) damage exposes collagen, Von Willebrand Factor, and other proteins to which platelets have receptors.
After platelet aggregation has occurred at a site of injury what happens?
There is then secretion of various chemicals from the platelets (eg ADP, thromboxane A2), which leads to aggregation of platelets at the site of injury.
What are the 3 main stages (3 A’s) in the formation of a platelet plug?
- Adhersion
- Aggregation
- Activation
Describe what happens in adhesion.
Platelets bind to subendothelial collagen via glycoprotein 1b and vWF.
Describe what happens in aggregation.
Platelets attach to each other via GPIIbIIIa and fibrinogen
Describe what happens in activation.
Platelets alter their shape to expose more phospholipid on the surface-provides a greater surface area for coagulation activation and fibrin production to stabilise the clot.
Granules release TXA2, thrombin and ADP to further recruit platelets
What is the activation stage augmented by?
Release of granules that further stimulate platelet activation – e.g. thrombin, thromboxane A2 and ADP – in order to recruit more platelets to the process.
What does the activation stage occur via?
Receptors to ADP etc. on the platelet surface
How does Aspirin work?
By inhibiting cyclo-oxygenase. (can no longer convert arachidonic acid to prostaglandins which are then converted to TXA2 which is then blocked from activated platelet aggregation)
Why does aspirin lead to an anti-platelet function?
COX is necessary to produce Thromboxane A2.
What is thromboxane A2?
A platelet agonist released from granules on activation.
What are the main side effects of aspirin?
- Bleeding.
- Block of prostaglandin production leads to:
- GI ulceration.
- Bronchospasm, especially in pts with asthma.
How do CLOPIDOGREL and PRASUGREL work?
They are ADP receptor antagonists.
How does dipyridamole work?
It is a phosphodiesterase inhibitor – reduced production of cAMP which is ‘second messenger’ in platelet activation.
Give an example of a new anti platelet drug.
Abciximab
How do new anti platelet drugs work?
GPIIb/IIIa inhibitors - inhibit aggregation
Platelets attach to each other via GPIIbIIIa and fibrinogen
When are new anticoagulants given?
These are very potent, so are given IV in heart surgery/angioplasty.
How long do anti-platelet drugs tend to affect platelet function for?
7-10 days - this makes sense as the lifespan of platelets is 7-10 days
Prior to elective operations, when should anti-platelet agents be stopped?
7 days prior
If serious (life-threatening) bleeding, how can the action of anti-platelets be reversed?
Give a platelet transfusion
