Thrombosis 1 Flashcards
Atherosclerosis + Arterial Thrombosis = ______
atherosclerotic lesion superimposed with thrombus formation
Atherothrombosis
What are 7 risk factors of atherothrombosis?
- Age (biggest risk factor)
- Male
- Family history
- Smoking
- Diabetes
- Cholesterol
- Hypertension
Atherothrombosis is an _______ disease of the ______ wall.
Atherothrombosis is the major cause of _________
Inflammatory, arterial
Acute Coronary Syndromes (ACS)
What are the 3 types of Acute Coronary Syndromes?
- Acute Myocardial Infarction
- Unstable Angina
- Ischaemic Sudden Death
___ % of strokes are due to blood clots, ___ % are due to haemorrhage.
85%, 15%
What are the 2 main types of CVAs?
- Stroke (neurological impairment > 24hrs)
2. Transient Ischaemic Attack (neurological impairment < 24hrs)
What are the 5 main stages of atherothrombosis formation/pathogenesis?
- Endothelial disruption: inflammation from smoking, cholesterol etc. Leukocytes adhere.
- Fatty streak formation: platelets, leukocytes, foam cells + smooth muscle migrate
- Advanced complicated lesion: necrotic core + fibrous cap forms, macrophages accumulate here too
- Unstable fibrous plaque: large fatty core, thin fibrous cap - prone to rupture, haemorrhage from plaque microvessels
- Rupture, thrombosis, vessel occlusion
What are the 3 steps in which platelets migrate to and bind to endothelium?
Good diagram on Slide 14
Following this what are the 2 steps that occur between the platelet and endothelium which allows the formation of an atherogenic-promoting environment to be made.
Good diagram on Slide 15.
- Activated endothelium expresses P-selectin
- Receptors on the surface of platelets (GPIb + PSGL-1) bind to this P-selectin on the endothelium - this is known as ROLLING (1st mechanism)
- Following this, beta3 integrins (also found on the platelet) then cement this bond - this is known as FIRM ADHESION (2nd mechanism).
- Inflammation then results as the platelets inflame the endothelial cells. The firm adhesion that has occurs causes the platelet itself to express P-selectin on its surface as well as secrete THROMBOGENIC FACTORS CD40L + IL-1beta. These platelets also attach + activate monocytes. These monocytes release lots of chemicals (proinflammatory cytokines, proteases etc) which allows the development of the prothrombotic core.
- The result of step 4 causes the endothelial cells to change to provide an inflammatory environment in which atherogenesis is promoted.
What are 2 treatment options for atherosclerosis?
- Healthy lifestyle: reduce cholesterol, lose weight, control diabetes, stop smoking, treat hypertension
- Statins
What are 2 treatment options for arterial thrombosis?
- Chronic therapy - aspirin (1st line), clopodegril (2nd line) (bleeding = major side effect) - usually these 2 are used at the same time
*** Overall, WEAK anti-thrombotic effect
These 2 meds are inhibitors of platelet ACTIVATION - Acute therapy - GPIIa/IIb inhibitors (GPIIa/IIb thought of as the ‘final common pathway in platelet aggregation’ - stops platelets aggregating) (bleeding = major side effect)
*** Overall, POWERFUL anti-thrombotic effect
These 2 meds are inhibitors of platelet ADHESION
Atherothrombosis is a diffuse disease that starts early in life and can then progress asymptomatically as the person ages. When it does start to show symptoms, it usually manifests as 1 of 3 diseases. What are they?
- ACS
- Stroke (Cerebrovascular Accident)
- Peripheral Arterial Occlusive Disease (PAOD)
What are 2 consequences of Peripheral Arterial Occlusive Disease (POAD)?
- Claudication - pain in calves
2. Ischemia, rest pain, gangrene
Atherothrombosis begins with endothelial dysfunction. At which parts in the body does this dysfunction normally occur at?
Arterial branch points associated with disturbed blood flow.
3 differences between HAEMATOSIS + THROMBOSIS?
- Haematosis = a normal clotting mechanism
Thrombosis = a blood clot, an exaggerated form of haematosis that usually occurs on the surface of a ruptured plaque. - H: endothelial cells are non-reactive to platelets
T: they are - H: doesn’t require fibrin generation
T: consolidated by fibrin generation
H: you’re literally trying to plug the hole in a vessel - blood stops as it is clogged
What are 6 disadvantages of ASPIRIN use to treat arterial thrombosis?
- Weak anti-thrombotic affect
- Risk of bleeding
- Not all patients respond to aspirin
- Doesn’t inhibit the initial adhesion of platelets
- The role of aspirin is to stop platelet activation. However platelets can be activated through a number of different routes. Aspirin doesn’t stop this alternate platelet activation.
- Doesn’t stop platelets expressed thrombogenic agents
