Haemostasis Flashcards
What is haemostasis?
The body’s reaction to injury or bleeding, formations of blood clots to prevent blood loss
What are the stages of haemostasis?
- Contraction of the blood vessel
- Unstable platelet plug formation (primary)
- Stabilisation of unstable platelet plug (secondary)
What 2 glycoproteins does platelet plasma membrane contain?
GP1a and GP1b
How do GP1a and GP1b work in forming a platelet plug?
When a vessel is damaged the GP1a can bind to the wall directly
GP1b binds to circulating von Willebrand factor which then binds to the wall of the damaged vessel
What physical change occurs when platelets use their glycoproteins to bind to the vessel wall or VWF and why?
They change from a disc shape to a more spherical shape with spicules, which help the platelets clump and form an unstable platelet plug
They also release the contents of their storage granules
What granules are present in platelets?
Alpha-granules and dense-granules
What is contained in the granules within platelets?
ADP, fibrinogen and VWF
How do the granules get released?
The platelet membrane invaginates, forming a passage to the surface of the cell
How does vasoconstriction occur in the first stage of haemostasis?
Arachidonic acid fromt eh membrane of the platelets is used to produce thromboxane A2, a vasoconstrictor
What does the release of ADP and thromboxane cause?
It causes a positive feedback loop, alongside thromboxane A2, which stimulates platelet activation and aggregation
The ADP binds to P2Y12 and thromboxane A2 to the thromboxane A2 receptor which causes the GP2b/3a receptor to change shape and become capable of binding to fibrinogen
What happens when fibrinogen binds to the activated GP2b/3a?
This further causes platelets to link together due to them binding to fibrinogen (primary haemostasis)
What does prostacyclin do?
It causes vasodilation and suppresses platelet activation, stopping them from aggregating when the blood doesnt need to clot
What does aspirin do?
Irreversibly inhibits the cyclo-oxegenase(COX) enzyme required for the production of thromboxane A2, therefore prevents platelet aggregation
Which factor does VWF carry?
Factor VIII
How is a unstable platelet plug stabilised?
- Blood coagulation produces thrombin
2. Thrombin cleaves fibrinogen to form a fibrin clot, stabilising the platelet plug
What clotting factors arent produced by the liver?
Factor VIII and VWF
Which clotting factors require vitamin K to become activated?
Factors II, VII, IX, X
Where do clotting factors work?
On the phospholipid membrane of platelets
How does Heparin work?
It indirectly helps antithrombin work better so antithrombin can inactivate factors Xa and IIa(thrombin) quicker. Can be given intravenously or subcutaneously
How does Warfarin work?
It is a vitamin K antagonist so stops factors II, VII, IX, X from becoming functional. Taken orally, taken in emergency as no need to monitor
How do direct oral anticoagulants work?
They directly inhibit IIa or Xa
How does flibrinolysis occur?
Tissue plasminogen activator(t-PA) and plasminogen come together on the clot by binding to fibrin, then plasminogen is converted to plasmin which breaks down fibrin to form Fibrin-degradation products
What does tranexamic acid do?
Binds to plasminogen preventing it from binding to fibrin so it cannot convert into plasmin = no fibrinolysis
What is thrombosis?
The formation of a clot in a stable vessel
