Haemostasis Flashcards
In tact endothelial function is needed for normal circulation.
Which naturally occurring substances prevent thrombus formation on an intact endothelium? (5)
- Nitric oxide
- Prostacyclin
- Heparans
- Tissue factor pathway inhibitor (TFPI)
- Thrombomodulin
What happens when you cut yourself?
- You bleed at the site of the injury
- The bleeding stops and you form a clot => Platelets, vWF, Coagulation Factors
- The clot remains confined to the site of injury => natural Anticoagulants
- And then about 1 week later the clot has vanished => Fibrinolytic System
When there is damage to the endothelial lining a clot is required.
Q. What are the 2 key signals that let resting platelets and coagulation factors know that they need to become activated to start the process of clot formation?
Abnormal surface – damaged vessel wall leads to rough collagen surface and the platelets recognise this abnormal surface and stick to it to plug the hole
Physiological activator - tissue factor - when you damage a blood vessel you release a small amount of the normal physiological activator of coagulation into the circulation
How are endothelial cells connected to subendothelial collagen?
By Von Willebrand factor (VWF)
What important structures do platelets have on their surface that helps them to do their job in clot formation? (2)
Cell surface receptors:
- ADP receptor
- Epinephrine receptor
- Thrombin receptor
When erythrocytes and endothelial cells are damaged they release ADP and Epinephrine into the circulation and form thrombin. These then bind to receptors on the platelet surface and allow it to behave normally and make a clot.
Platelet glycoproteins
These are binding sites for important ligands that are involved in coagulation such as:
- GP 2b/3a = fibrinogen
- GP 1b/5/9 = VWF
- GP 1a/2a and GP 6 = collagen
Platelets have an open canalicular system. What is meant by this?
- Platelets have canals that allow the content of the platelet to be released into the circulation.
- Within platelets there are dense and alpha granules and lysosomes that are released into the circulation as required to perform different functions.
- When platelets are activated the actin and myosin within contracts and squashes the cell, pushing the granules out through the canals onto its surface which makes it sticky.
What do dense granules produce? (3)
- ADP/ATP
- Calcium
- Serotonin
What do alpha granules produce? (2)
- Thrombin
- VWF
What are the 3 A’s in haemostasis?
- Adhere
- to collagen through GP 1a and GP 6
- to fibrinogen through GP 2b/3a
- to vWF through GP 1b
- Activation
- p2y12 pathway - activated by ADP that is released by damaged cells/tissues
- COX pathway - produces thromboxane which results in platelet aggregation
- Aggregation
- Thromboxane causes the platelets to aggregate
Which drug interferes/blocks the Cyclooxygenase (COX) pathway to prevent production of thromboxane?
Aspirin - prevents thromboxane production which prevents platelet aggregation (prevents the stickyness of platelets basically)
What is the p2y12 pathway?
- p2y12 is a chemoreceptor on the surface of platelets in which ADP binds to, triggering reactions within the cell.
- The P2Y12 receptor is involved in platelet aggregation
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Which drugs inhibit/block the p2y12 pathway? (3)
- Clopidogrel
- Prasugrel
- Ticagrelor
These are commonly used in patients who have had a STEMI or PCI
When people speak about dual anti-platelet therapy what are they referring to?
The use of aspirin with one of the p2y12 inhibitors therefore blocking both the COX and p2y12 pathways
What does the enzyme scramblase do and why is it important?
Scramblase allows the phopholipid layer to be expressed on the external surface to act as a site for coagulation reactions can take place on
Why is vWF so important in clot formation?
vWF is basically a big sticky molecule that you want around when making a clot because:
- It binds to factor 8 which you always want to make a clot
- It binds to the surface of platelets through GP 1b
- It binds to collagen through a couple of receptor sites