Haemostasis Flashcards
What does the endothelium produce?
- Heparins
- TFPI
- Thrombomodulin
- Prostacyclin
- Nitric oxide
What is the key job of the endothelium?
- Prevent cells sticking to the walls
- Encourage flow
What happens when you cut yourself?
- You bleed at the site of injury
- It stops and a clot forms
- The clot remains confined to the site of injury
- 1 week later the clot has vanished
What is clotting dependent on?
- Platelets
- vWF factor
- Coagulation factors
Why does the clot remain confined to the site of injury?
So that the whole system does not become occluded.
This is done by anti-coagulants
How is the clotting system activated?
- Resting platelets and coagulation factors are activated by signals and localised to the area of damage
- These signals include abnormal wall surface and physiological activators
- Vessel damage leads to platelet adhesion
What receptors are present on the surface of platelets?
- ADP receptor
- Epinephrine receptor
- Thrombin receptor
What granules are present in platelets?
- Alpha granule
- Dense granule
What do alpha granules produce?
- VWF
- Thrombin
What do dense granules produce?
- ATP
- Calcium
- Serotonin
What do the glycoprotein receptor on the surface of platelets binds to?
Some bind to:
- Collagen and the vessel wall
- von Willbrand factor
- Fibrinogen
What role do platelets play in haemostasis?
- Adhere to area of damage
- Activate EDP pathway and cylo-oxygenase pathway
- Aggregate
- Provide a phospholipid surface for coagulation
- Form a plug with fibrinogen in primary haemostasis
What forms the primary haemostatic clot?
Platelets
What forms the definitive haemostatic clot?
Fibrin
What is the clotting factor cascade which activates clot formation?
- Factor XII
- Factor XI
- Factor IX
- Factor VIII
- Factor X
- Prothrombin
- Fibrinogen
What prevents the clotting cascade?
Anticoagulants
Where is the defect in haemophilia A?
Factor IX is deficient
Where is the defect in haemophilia B?
Factor VIII is deficient
How is tissue factor produced?
Produced by damaged tissues
Give examples of natural anticoagulants and what they target.
- Tissue factor pathway inhibitor
- Binds to and inactivates the activated factor X and VII
- Protein C and S
- Inactivates activated factor V and VIII
- Antithrombin
- Inactivates activated factor X and thrombin
What is fibrinolysis?
Process in which clots are broken down
How does fibrinolysis occur?
- Endothelium produces activators of plasminogen: t-PA and u-PA
- Plasminogen is cleaved to active plasmin
- Plasmin breaks the clot down resulting in fibrin degradation products including D-dimer
What ensures there is not too much fibrinolysis?
Inhibitors of plasminogen and plasmin
What is the mechanism of clopidogrel and ticagrelor?
Acts on the EDP pathway
What is the mechanism of warfarin?
- Reduces the amount of coagulation factors 2,7,9 and 10 (vitamin K dependent)
- It inhibits vitamin K
What is the mechanism of riveroxaban?
Target factor X and inactivate it
What is the mechanism of dibigatran?
Oral inhibitor of thrombin
What is the mechanism of heparin?
Increases ability of anti thrombin
