Flashcards in Haemostasis Deck (44)
State the steps involved in haemostatic plug formation from the time of injury.
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.
Von Willebrand Factor
What process during maturation of the megakaryocytes is important for the formation of platelets?
How many platelets are produced by one megakaryocyte?
What do the dense granules in platelets contain that is important for platelet function?
What do alpha granules in the platelets contain?
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?
These bind to fibrinogen
What else can activate platelets?
Which enzyme converts phospholipids to arachidonic acid?
What does COX convert arachidonic acid to?
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.
State two ADP receptor antagonists.
State three GlpIIb/IIIa antagonists.
What is the most important test for monitoring platelets and their function?
What is a common cause of spontaneous bleeding?
Autoimmune thrombocytopenia (autoimmune antibodies clear platelets from the circulation)
This results in purpura, multiple bruises and ecchymoses
What is the normal range for platelet count?
150-400 x 109/L
Why do you get thrombocytopenia in leukaemia?
Leukaemic cells populate the bone marrow so it crowds out the megakaryocytes so the platelets aren’t produced in sufficient numbers
What is the bleeding time test used to observe?
This checks the platelet-vessel wall interaction
This isn’t used any more
Describe the platelet aggregation test.
The platelets are stimulated with ADP/thromboxane/collagen to study their function
This is used to diagnose platelet disease e.g. von Willebrand disease
Where is von Willebrand factor produced?
Endothelial cells and a little bit by megakaryocytes
What factors do megakaryocytes produce?
Von Willebrand Factor
Tissue factor activates the clotting cascade by converting 9 to 9a and by converting 10 to 10a. What difference does this make?
9 to 9a – slower but produces more thrombin
10 to 10a – faster
State two accelerating factors. What are they activated by?
They are activated by trace amounts of thrombin
Which factors are activated on the surface of the platelet? Describe how this works.
10 to 10a
2 to 2a (prothrombin to thrombin)
For 9a to activate 10 it needs to come in close proximity with 10. They both bind to the surface of the platelet mediated by calcium ions, andfactor VIIIa bring the two close together so that 9a can proteolytically cleave 10 to 10a
Factor Va does the same with 10a and 2 (prothrombin)