Haemostasis Flashcards
State the steps involved in haemostatic plug formation from the time of injury.
Vessel constriction
Formation of an unstable platelet plug (platelet adhesion + platelet aggregation)
Stabilisation of plug with fibrin (blood coagulation)
Dissolution of clot and vessel repair (fibrinolysis)
What component found underneath the endothelium is involved in triggering the coagulation cascade?
Procoagulant subendothelial structures e.g. collagen Tissue factor is also expressed on the surface of the cell that underlie blood vessels but it is NOT normally expressed within the circulation itself
State some important factors produced by endothelial cells.
Prostacyclin
Thrombomodulin
Von Willebrand Factor
Plasminogen Activator
What process during maturation of the megakaryocytes is important for the formation of platelets?
Granulation
How many platelets are produced by one megakaryocyte?
4000
What do the dense granules in platelets contain that is important for platelet function?
ADP
What do alpha granules in the platelets contain?
vWF
Factor V
State the two ways in which platelets can bind to collagen. Name the receptors involved.
It can bind via vWF to collagen (via the GlpIb receptor)
It can bind directly to the collagen (via the GlpIa receptor)
What happens following the passive adhesion of platelets andengagement of receptors?
The receptors signal inside the cell to release ADP from the storage granules and to synthesise thromboxane
These bind to receptors on the surface of the platelets and activate them
Once activated, GlpIIb/IIIa receptors become available, which can bind to fibrinogen and allows the platelets to aggregate
Which receptors on the platelets become available following activation of the platelets and what do they bind to?
GlpIIb/IIIa
These bind to fibrinogen
What else can activate platelets?
Thrombin
Which enzyme converts phospholipids to arachidonic acid?
Phospholipase
What does COX convert arachidonic acid to?
Endoperoxides
Describe what happens to endoperoxides in platelets and in the endothelial cells.
Platelets – thromboxane synthetase converts endoperoxides to thromboxane (potent inducer of platelet aggregation)
Endothelial Cells – prostacyclin synthetase converts endoperoxides to prostacyclin (important regulator of haemostasis)
What effect does aspirin have on this entire pathway? What effect does aspirin have on this entire pathway?
Aspirin is a COX1 inhibitor
State some important drug targets in platelet aggregation.
COX
GlpIIb/IIIa
ADP Receptor
State two ADP receptor antagonists.
Clopidogrel
Prasugrel