Arterial Thrombosis and Anti-Platelets Drugs Flashcards
(24 cards)
Explain the formation of arterial thrombosis
High P system causes atherosclerosis; the thrombus is platelet-rich
Treatment of arterial thrombosis?
Aspirin and other anti-platelet drugs modify risk factors for atherosclerosis
Process of atherosclerosis?
- Damage to endothelium
- Recruitment of ‘foamy’ macrophages rich in cholesterol
- Forms plaques rich in cholesterol
Structure of stable atherosclerotic plaques?
Hyalinised and calcified
Conditions involving stable plaques?
Stable angina (coronary artery)
Intermittent claudication (leg artery)
Why are unstable atherosclerotic plaques dangerous?
Plaques rupture, platelets are recruited and cause acute thrombosis, e.g: MI and stroke (sudden onset of symptoms); leads to acute organ ischaemia and infarction
How does arterial thrombosis develop?
Plaque rupture - more likely in the high P environment of arteries
Platelet adhesion - exposed endothelium and release of vWF
Platelet activation - release granules that activate coagulation and recruit other platelets to developing platelet plug
Platelet aggregation - via membrane glycoproteins
Risk factors for arterial thrombosis?
Factors that cause damage to endothelium, increase in foamy macrophages and platelet activation:
• Hypertension damages endothelium and platelet activation
• Smoking damages endothelium and platelets
• High cholesterol accumulated in plaque
• DM (endothelium, platelets, cholesterol)
Prevention of arterial thrombosis?
Stop smoking
Treat hypertension and diabetes
Lower cholesterol
ANTI-PLATELET DRUGS
What are platelets?
Platelets are small anucleate discs with a mean life-span of 7 to 10 days
Formation of platelets?
Platelets are formed in the bone marrow by ‘budding’ from megakaryocytes
How does the platelet plug form?
Platelet adhesion at the site of injury
Platelet aggregation
Platelet activation
How does platelet adhesion occur?
Endothelial damage exposes collagen, vWF and other proteins to which platelets have receptors; platelets bind to sub-endothelial collagen via glycoprotein 1b and vWF
How does platelet aggregation occur?
Secretion of various chemicals from the platelets, e.g: ADP, thromboxane A2; platelets attach to one another via glycoprotein IIB/IIIa and fibrinogen
How does platelet activation occur?
Platelets alter their shape to expose more phospholipid on the surface, providing a greater SA for coagulation activation and fibrin production to stabilise the clot
This is augmented by release of granules, e.g: thrombin, thromboxane A2 and ADP, which further stimulate platelet activation and recruit more platelets; this occurs via receptors to ADP on teh platelet surface
Types of anti-platelet drugs?
Aspirin
Clopidogrel, prasugrel
Dipyridamole
Abciximab
MoA of aspirin?
Inhibits COX, which is necessary to produce thromboxane A2 (a platelet agonist released from granules on activation)
Normal function of COX?
COX converts arachidonic acid into PGs
PGs are then converted into thromboxane A2 (causes platelet aggregation)
Side effects of aspirin?
Bleeding
Blocks production of PGs:
• GI ulceration
• Bronchospasm
NOTE - caution in patients with asthma (Samter’s triad - asthma, recurrent sinus disease with nasal polyps and aspirin/NSAID sensitivity)
MoA of clopidogrel and prasugrel?
ADP receptor antagonists
MoA of dipyridamole?
Phosphodiesterase inhibitor - reduces production of cAMP, which is a 2nd messenger in platelet activation
MoA of abciximab?
GP IIb/IIIa inhibitor
It inhibits platelet aggregration
NOTE - these are rarely used, as they are very potent; they are administered IV in certain situations, e.g: angioplasty, cardiac surgery (sometimes)
Stopping anti-platelet drugs for elective surgery?
Anti-platelet drugs tend to affect platelet function for their 7-10 day lifespan
So, stop anti-platelet agents 7 days prior to elective operations
What to do if a patient on anti-platelets has a serious bleed?
Can reverse with platelet transfusion
