Arterial Thrombosis and Anti-platelet Drugs Flashcards
what are antiplatelets used for?
arterial atherosclerotic events causing a platelet rich thrombus due to rupture
arterial thrombosis vs atherosclerosis?
atherosclerosis = the plaque
thrombosis occurs after the plaque ruptures and platelets aggregate at the site forming a thrombus
how does atherosclerosis form?
damage to endothelium > recruitment of foamy macrophages rich in cholesterol > cholesterol rich plaque forms
describe stable atherosclerotic plaques
hyalinised and calcified
what do stable atherosclerotic plaques cause?
stable angina (coronary artery) intermittent claudication (leg artery)
what does unstable atherosclerotic plaque cause?
plaque rupture > recruitment of platelets and acute thrombosis
can cause unstable angina and MI with sudden onset of symptoms
can cause stroke
(generally organ ischaemia and infarction)
how is hypertension involved in atherosclerosis?
can cause the initial injury inducing formation of the plaque
high pressure system also makes the plaque more likely to rupture
how does an acute thrombosis form?
platelet adheres to exposed endothelium and release of vWF
platelets become activated and release granules that activate coagulation and recruit other platelets to developing platelet plug
platelet aggregation via membrane glycoproteins
risk factors for arterial thrombosis?
factors which cause damage to endothelium, increase in foamy macrophages or platelet activation
- hypertension
- smoking
- high cholesterol
- diabetes mellitus
how can arterial thrombosis be prevented?
stop smoking treat hypertension treat diabetes lower cholesterol anti-platelet drugs
how are platelets formed?
budding off from cytoplasm of megakaryocytes in bone marrow
structure of platelet?
no nucleus
disc shaped
have receptors for vWF and other proteins exposed at site of ruptured plaque
secrete various chemicals which lead to aggregation of platelets
what chemicals to platelets secrete?
ADP
thromboxane A2
lifespan of platelets?
7-10 days
describe platelet adhesion
platelets bind to exposed subendothelial collagen via glycoprotein 1b and vWF
describe platelet aggregation
platelets attach to each other via glycoprotein 2b and 3a and fibrinogen
what happens at the same time as aggregation?
activation
describe platelet activation
platelets alter their shape to expose more phospholipid on the surface which gives a bigger surface area for coagulation activation and fibrin production to stabilise clot
process is augmented by release of granules that further stimulate platelet activation in order to recruit more platelets to the process (occurs via receptors to ADP etc on the platelet surface)
how does aspirin work?
inhibits cyclo-oxygenase which is necessary to produce thromboxane A2
side effects of aspirin?
bleeding
also blocks production of prostaglandins in the stomach which protects against gastric HCl therefore the stomach isn’t protected and ulceration can occur
can also cause bronchospasm
how do clopidogrel and prasugrel work?
ADP receptor antagonists
how does dipyridamole work?
phosphodiesterase inhibitor
reduces production of cAMP which is a second messenger in platelet activation
which antiplatelet drug inhibit glycoprotein 2b and 3a?
abciximab
- inhibits aggregation of platelets
how can bleeding risk be managed with antiplatelets?
anti platelets affect platelet function for their 7-10 day lifespan
should therefore be stopped 7 days prior to elective operations
action can be reversed with platelet transfusion if serious bleeding occurs
which is inflammatory, arterial or venous thrombosis?
arterial
which causes organ ischaemia?
arterial
