Week 3 - F - Arterial thrombosis & anti-platelets - Platelet Adhesion/Aggregation - Aspirin/Clopidogrel/Prasgruel/Dipyridamole/GPIIbIIIa Flashcards
What are the main groups of arteries affected in arterial thrombosis? What are the main things affected in venous thrombosis?
Arterial thrombosis - coronary, cerebral and peripheral arteries Venous thrombosis - mainly DVT and PE
Arterial system relies on the muscular arterial wall to pump blood around Venous system relies on mainly the calf muscles to push blood back up to heart Arterial thrombi usually start of due to astherosclerosis How does astherosclerosis occur? How does it end up in a blood clot?
Damage to the endothelium of the arteries causes the recruitment of foamy macrophages which are rich in cholesterol causes the build up of an atheromatous plaque Rupture of the plaque causes platelet recruitment to form a clot - this is the thrombosis
What symptoms do stable atherosclerotic plaques cause? Ie if in the heart or in the leg
Can cause angina if in the cornary circulation or Intermittent claudication if in the peripheral arteries - leg Both symptoms usually occur on exercise
When the plaque ruptures, the damaged endothelium shows collagen causing platlets to bind here and the vWF also binds the platelets Once the platelets are bound, platelet aggregation occurs via the release of different granules Name two of the compounds platelets released to cause platelet aggregation?
TXA2 (thromboxane A2) and ADP (adenosine diphosphate) are released by the platelets to stimulate further platelet aggregation to the site of injury This occurs by these granules that are released binding to their specific receptors on other platelets
Name four risk factors for arterial thrombosis? ie Factors that cause damage to endothelium, increase in foamy macrophages and platelet activation:
Hypertension - damages endothelium and platelet activation Smoking - damages ednothelium and platelet activation Hyperlipidaemia - high cholesterol - this is what makes up the atherosclerotic plaque Diabetes - damages the endothelium, platelet activation and cholesterol
What were the treatment options for venous thrombosis again? What are venous thrombosis due to?
LMWH, Warfarin, New oral anti-coagulants (rivoroxaban/apixaban - Xa inhibitor or dabigatran (IIa inhibitor) Venous thrombosis are due to defects in the stasis of blood, endothelium and hypercoaguablitiy - this is known as Virchow’s triad
Platelets are formed in the bone marrow by ‘budding’ from megakaryocytes What is the mean life-span of the platelet? Does a platelet have a nucleus?
The mean life span of a platelet is 7-10 days Platelets are small anucleate discs
When there is endoethelial damage exposing the subendothelial collagen, what helps bind platelets to this? One of the answers is a platelet surface protein
Platelets bind to the subendoethelial collagen via glycoprotein Ib which binds to vWF This is platelet adhesion
What is the rare autosomal recessive bleeding disorder that causes a deficiency of glycoprotein Ib (GpIb), the receptor for von Willebrand factor known as?
This is Bernard Soulier syndrome These mutations do not allow GPIb-IX-V complex to bind to the von Willebrand factor, which in turn is what would help platelets adhere to a site of injury which eventually helps stop bleeding.
What is it that is released that helps the platelets to aggregate? What is the receptors via which platelets will then bind to one another?
Platelets releases TXA2 and ADP among other granules to cause platelet aggregation The GPIIBIIIA receptor allows platelets to bind to one another - fibrinogen molecule binds these receptors to each platelet causing formtation of the soft platelet plug
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. What are the drug types used to treat arterial thrombosis by reducing the platelet levels?
This would be antiplatelets
Try and name 4 different types of anti-platelets
Aspirin Clopidogrel Prasgruel Dipyridamole
What is the mode of action of aspirin and its side effects?
This inhibits the cyclo-oxygenase 1 (COX-1) enzyme which plays a role in the arachdonic pathway release of thromboxane A2 - therefore this prevents platelet aggregation Bleeding Prostoglandin inhibition leads to both GI ulceration & Bronchospasms (not given in asthmatics)
How do clopidogrel, prasgruel and dipyridamole work?
Clopidogrel and prasgruel both work by inhibiting ADP receptors (ADP receptor antagonists) Dipyridamole works by inhibtiing phospodiesterase inhibitor
What is the receptor which clopidogrel/prasgruel inhibit the binding of ADP to known as? What is the function of phosphoidesterase for platelets?
ADP binds to the receptor P2Y12 And therefore clopidogrel or prasgruel can be known as ADP receptor inhibitors or P2Y12 inhibitors Phosphodiesterase increase cAMP which is a ‘second’ messenger in platelet activation and dipyridamole inhibits this - phosphodisterase inhibitor
ADP receptros antagonisits allow ADP to be produced as normal but prevet the ADP binding to the surface of the platelet and therefor epaltelet aggregation cannot be signalled Aspirin actually blocks the synthesis of TXA2 – thromboxane inhibitor as it blocks the cyclooxygenase 1 enzyme There is another type of antiplatelet known as GPIIbIIIa inhibitors What does this do? Name one type?
GPIIbIIIa was the receptors on the platelet surface to allow platelets to bind to one another Inhibition of this impacts on platelet aggregation as well An example is abciximab
How long do anti-platelet drugs tend to affect platelet fucntion and therefore how long before operation must they be stopped?
Antiplatelet drugs tend to affect platelet function for their whole life span as they affect platelets for 7-10 days and therefore should be stopped at least 7-10 days before surgery eg If want to get rid of the anti-platelet effect prior to operation, stop aspirin 1week prior, therefore will be all the platelets are new
