Haemostasis Flashcards
(58 cards)
State the 4 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 + vessel repair (fibrinolysis)
What component found underneath the endothelium is involved in triggering the coagulation cascade?
Procoagulant subendothelial structures e.g. collagen
Tissue factor expressed on surface of cells underlying blood vessels but it is NOT normally expressed within the circulation
What process during maturation of megakaryocytes is important for formation of platelets?
Granulation
How many platelets are produced by 1 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
Growth factors
Fibrinogen
State the 2 ways in which platelets can bind to collagen. Name the receptors involved.
Via vWF to collagen (via GpIb receptor)
Bind directly to the collagen (via GpIa receptor)
What happens following the passive adhesion of platelets and engagement of receptors?
Receptors signal inside the cell to release ADP from storage granules + to synthesise thromboxane
These bind to receptors on the surface of platelets + activate them
Once activated, GpIIb/IIIa receptors become available, which can bind to fibrinogen + allows platelets to aggregate
Which receptors on the platelets become available following activation of the platelets and what do they bind to?
GlpIIb/IIIa
Bind to fibrinogen
What else can activate platelets?
Thrombin
What is the most important test for monitoring platelets and their function?
Platelet count
What is a common cause of spontaneous bleeding?
AI thrombocytopenia (AI antibodies clear platelets from the circulation) Results in purpura, multiple bruises + ecchymoses
What is the normal range for platelet count?
150-400 x 10^9/L
Why do you get thrombocytopenia in leukaemia?
Leukaemic cells populate the BM which crowds out megakaryocytes so platelets aren’t produced in sufficient numbers
What is the bleeding time test used to observe?
Checks the platelet-vessel wall interaction
Isn’t used any more
Describe the platelet aggregation test.
Platelets stimulated with ADP/thromboxane/collagen to study their function
Ued to diagnose platelet disease e.g. von Willebrand disease
Where is von Willebrand factor produced?
Endothelial cells + a little by megakaryocytes
What factors do megakaryocytes produce?
Factor V
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 2 accelerating factors. What are they activated by?
Factor VIII
Factor V
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, + factor 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)
Which factors are affected by warfarin?
2, 7, 9, 10
What is common to factors 2, 7, 9 + 10 and what is the significance of this common feature?
Have a cluster of glutamic acid
-recognised by liver enzyme + undergoes post-translational modification in the presence of vitamin K to Gamma-carboxyglutamic acid (Gla)
Once this extra carboxyl group is added, calcium can facilitate the binding of Gla to the activated platelet membrane phospholipid
How does warfarin actually inhibit the post-translational modification of factorsn 2, 7, 9 + 10?
Warfarin inhibits vitamin K epoxide reductase thus inhibiting the gamma carboxylation of factors 2, 7, 9 + 10
