thrombosis Flashcards
what is an arterial thrombosis?
a thrombosis in a high pressure system (arteries)
a platelet rich thrombus as a result of atherosclerosis
what is atherosclerosis?
damage to the endothelium, recruitment of cholesterol rich ‘foamy’ macrophages and formation of cholesterol plaques
o Stable plaques – hyalinised and calcified
- Stable angina, intermittent claudication
o Unstable atherosclerotic plaques
- Plaques rupture, platelets are recruited and cause acute thrombosis
- Sudden onset of symptoms – acute organ ischaemia and infarction
- Unstable angina or myocardial infarction (coronary arteries)
- Stroke (cerebral arteries)
how so arterial thrombus develop?
- Plaque ruptures – more likely in the high pressure environment of arteries
- Platelet adheres to it – exposed endothelium and release of Von Willebrand factor
- Platelets becomes activated - release granules that activate coagulation and recruit other platelets to developing platelet plug
- Platelet aggregation via membrane glycoproteins
what are the risk factors for arterial thrombosis?
factors which damage the endothelium, increase foamy macrophages and platelet activation o Hypertension (damage to endothelium, platelet activation) o Smoking (endothelium, platelets) o High cholesterol (accumulated in plaque) o Diabetes mellitus (endothelium, platelets, cholesterol)
how can arterial thrombosis be prevented?
o Stop smoking o Treat hypertension o Treat diabetes o Lower cholesterol o Anti-platelet drugs
how can arterial thrombosis be managed/further incidents prevented?
antiplatelets
• aspirin - Inhibits cyclo-oxygenase which is necessary to produce Thromboxane A2 (a platelet agonist released from granules on activation)
• Clopidogrel, prasugrel – ADP receptor antagonists
• Dipyridamole - Phosphodiesterase inhibitor - increases production of cAMP which inhibits platelet aggregation
• GP IIb/IIIa inhibitors – abciximab – inhibit aggregation (platelets attach to each other via GPIIb/IIIa and fibrinogen)
• modify risk factors for atherosclerosis
what are the side effects of aspirin?
bleeding
blocks production of prostaglandins
GI ulceration
Bronchospasm
bleeding risk on antiplatelets?
o anti-platelet drugs tend to affect platelet function for their 7-10 day lifespan
o stop antiplatelet agents 7 days prior to elective operations
o if serious bleeding can be reversed with platelet transfusion
what is the mechanism of platelet activation following endothelial damage?
- Endothelial (vessel wall) damage exposes collagen, Von Willebrand Factor (VWF), and other proteins to which platelets have receptors – platelet adhesion at the site of injury.
- 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 is platelet adhesion?
Platelets bind to subendothelial collagen via glycoprotein Ib and von Willebrand factor
what is platelet aggregation?
Platelets attach to each other via GPIIb/IIIa and fibrinogen
what is platelet 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.
Process is augmented by release of granules that further stimulate platelet activation eg Thrombin, Thromboxane A2 and ADP in order to recruit more platelets to the process.
This occurs via receptors to ADP etc on the platelet surface
what are the properties of a venous thrombosis?
- Low pressure system
- Platelets not activated
- Activates coagulation cascade – rich in fibrin clot
what are the conditions which lead to venous thrombosis?
Virchow’s triad
o Stasis
o Vessel wall
o Hypercoagulability
what are the risk factors for VTE?
DVT or PE,
stasis,
vessel wall
hypercoagulability
