L04-Platelets and coagulation Flashcards
What does the term clot refer to?
An intravascular thrombus
What does a haemostasic response involve normally?
Complex interactions between activated plasma clotting factors and platelets at the site of injury.
How are platelets produced?
They are produced by megakaryocytes in the bone marrow
What is the normal lifespan of a platelet?
8-12 days
What is the initial response to damaged endothelium?
Transient local vasoconstriction in order to reduce blood loss
What is the structure of a clot surrounding damaged endothelial tissue?
The inner shell consists of a dense inner core made up of fully activated platelets
This is surrounded by an outer shell of partially activated loosely packed platelets
What are the three main types of granules contained within platelets?
Dense granules - contain mediators of platelet activation such as serotonin, adp and calcium
Alpha granules - contain a number of clotting factors including FV, FVIII, fibrinogen, von Willebrand factor
Glycogen granules - provide the energy source for platelet reactions
Which are the two most important platelet glycoprotein receptors and what do they do?
GP1b - attaches to von Willebrand factor to form the initial tethering of the platelets
GPIIb/IIIa - is activated after tethering and expresses vWF which causes further platelets to tether and begins to form the clot
What are the inhibitors of coagulation?
Tissue factor pathway inhibitor (TFPI)
Antithrombin
Protein C
Protein S
What are two platelet inhibitors?
Prostacyclin
Nitric oxide
What initially activates platelets at damaged endothelium?
ADP released from damaged blood vessel endothelial cells. Along with exposed collagen and thrombin
How are blood coagulation factors synthesised and released?
They are synthesised in the liver and released into the circulation in inactive precursor forms
What vitamin is required for synthesising some of growth factors and which growth factors are these?
Vitamin K is required to synthesise prothrombin (factor II) F VII, IX and X
This is why it is given to all babies in hospitals as a deficiency can lead to bleeding tendencies
Which factors are cofactors in the coagulation cascade and for which factors?
FV is a cofactor for activated FX
FVIII is a cofactor for activated FIX
What is the result of ADP activating platelet metabolic pathways?
the release of dense and alpha granules which consolidates the platelet responce
What is von willebrand factors use other than for platelet adhesion?
It is a natural carrier of factor VIII
Where is von willebrand factor sythesised?
It is synthesised in blood vessel endothelial cells and megakaryocytes
Which factor initiates the cooagulation cascade and how does it go about doing this?
FVII initiates the cascade by becoming activated by binding to tissue factor which is exposed on damaged membranes.
What is the action of activated FVII?
It directly activates FX which with the help of FV converts prothrombin into thrombin
The thrombin formed by FXa is not generated in enough quantity to cause significant fibrinogen to fibrin conversion, what does the thrombin do instead?
It releases FVIII from vWF and activates it along with activating FXI and FV.
What is the final stage of the coagulation cascade?
Activated factors VII and XI generated activated FIX which with the aid of its cofactor FVIII it activates FX which generates sufficient thrombin to generate a clot.
After the initiation of coagulation which part of the cascade is inhibited?
the direct activation of FX by FVIIa which is inhibited by extrinsic pathway inhibitor (EPI)
What is bernard-soulier syndrome?
Deficiency of membrane GPIb
What is haemophillia A?
Deficiency of FVIII
