Platelets + thrombosis Flashcards
Describe the role of platelets in clotting
Think about:
What are platelets?
What is their function?
Describe the clotting mechanism (what is release reaction, platelet adhesion)
Non-nuclear cellular fragments
Form mechanical plugs during blood vessel injury
Adhesion and aggregation reactions :
- Adhesion: to subendothelial surface on damage/disease - due to binding to Von Willebrand’s factor
- Adhesion causes Release reaction: ADP and thromboxane which promote platelet Aggregation
Leads to platelet mass to plug area of endothelial damage = promotes coagulation reaction: -vely charged phospholipids on activated platelets which have adhered to site of damage localize fibrin formation
Coagulation involved in:
- Haemostasis - stopping blood loss (bleeding…to death) through damaged vessels
Define ‘platelet aggregation
clumping together of platelets in the blood
What is thrombosis?
Unwanted formation of blood clots
Can give you a stroke/heart attack
What is venous thrombosis?
Clots (thrombi) form in veins (DVT) due to stasis of blood (stoppage/slowdown of blood flow)
- May travel to lungs = pulmonary embolism*
- Venous thrombosis is ‘more’ of a coagulation factor event*
- DVTs (deep vein thrombosis)
How does atrial fibrillation cause thrombosis?
Blood clots can form in atria
Clots are pumped into circulation
Clots can go towards the brain
Patient at risk of TIA (transient ischaemic attack) - mini stroke
What is arterial thrombosis?
Form at atherosclerotic sites, lead to arterial blockage:
- heart (‘heart attack’, MI)
- cerebral vessels (stroke)
- Arterial thrombosis is ‘more’ of a platelet event*
- MIs and ischaemic strokes
Draw a simple pathway of the synthesis of prostacyclin and thromboxane from arachidonic acid
Describe the effects of prostacyclin on platelet aggregation
Endothelial (cells that line blood vessels) derived vasodilators + inhibits platelet aggregation
Prostacyclin (PGI2) - prevents platelet aggregation, acts on platelets to increase cAMP (good thing)
Thromboxane (TXA2) - promotes aggregation, decreases cAMP
Describe the effects of nitric acid on platelet aggregation
Endothelial (cells that line blood vessels) derived vasodilators
L-arginine + O2 => NO + citrulline
by nitric oxide synthase (enzyme)
Nitric oxide - prevents both platelet adhesion and aggregation by increasing platelet cGMP
Describe the antiplatelet effects of aspirin
Low dose Aspirin (75mg) quarter of original dose
Used to prevent MI in patients who have previously had an MI
- Recommended for secondary but not primary prevention
Reduces incidence of stroke
Inhibits cyclo-oxygenase (irreversible)
- Inhibits thromboxane (good)
- Also inhibits prostacyclin
Describe the antiplatelet effects of dipyridamole.
Antiplatelet drug
Phosphodiesterase inhibitor - prevents breakdown of cAMP + cGMP (which are broken down by phosphodiesterase)
Used to prevent thrombosis
Inhibits adenosine uptake
Used in conjunction with aspirin
Describe the antiplatelet effects of clopidogrel.
Clopidogrel focusses on GP IIb/IIIa (glycoprotein)
ADP from aggregating platelets leads to expression of GP IIb/IIIa
GP IIb/IIIa - binds fibrinogen which leads to cross-linking of platelets
Clopidogrel - inhibits ADP-induced expression of GP (ADP receptor antagonist)
- for pts that cannot take aspirin
- can be used with aspirin
- Clopidogrel + aspirin greatly reduce MI (CURE trial)
Abciximab - monoclonal antibody against GP IIb/IIIa
- given to pts undergoing angioplasty
- use once
Define the process of fibrinolysis + state the major components in the process
e.g. streptokinase, altopase
Drugs activates fibrinolysis (endogenous system to dissolve clots)
Activates plasminogen which forms plasmin
Plasmin - enzyme which digests fibrin of the clot
Fibrinolytic agents (clot busters) - activate plasminogen to plasmin conversion
State how drugs influence fibrinolysis + list the conditions where these drugs may be used
Used after MI - dissolve thrombus that caused blockage in coronary arteries
Used in angioplasty + pulmonary embolism
Thrombolytics (drugs used in fibrinolysis) used with aspirin (can caused bleeding)
Used in thromboembolic stroke (e.g. alteplase)
