Haemostasis and Inherited bleeding disorders Flashcards
what are the key components of haemostasis
- Platelets
- Von Willebrand factor
- Clotting proteins
what makes up primary haemostasis
- platelets and VWF dependent
what makes up secondary haemostasis
- fibrin
where are platelets derived from
- Non nucleated cytoplasmic fragments derived from bone marrow megakaryocytes
What is the structure of platelets
- 1-4um
- Cellular membrane is made out of lipid bilayer, cell membrane, and glcyorpotein receptors
- Lipid bilayer with underlying microtubular system – series of granules
- Multiple components in each granule – dense granule important agonists, alpha granules fibrinogen, FV, P selectin
- Platelet membrane – complex of at least 9 glycoproteins.
what is the average amount of platelets in the blood
- Reference range for platelets in blood 140 to 400-450x109/
what is the lifespan of a platelet
- 8 to 14 days
what system removes platelets from the blood
- Removed from the circulation by the reticuloendothelial system
describe what the cell membrane of a platelet it like
- glycoproteins molecules have receptors for agonist, adhesive, coagulation factors and other platelets
- the receptors that are most abundant are GPIIb/IIIa and Gp1b
- the cell membrane also contains phospholipids
- it is associated with prostaglandin synthesis, calcium mobilisation, localisation of coagulant activity to the platelet surface
what are the organelles in a platelet
- there are platelet specific granules such as
- dense osmophilic granules (dense bodies, d-granules)
- a granules are the glue that hold the platelets together
what are the substances that can be in a-granules
- VWF
- platelet factor 4
- b-thromboglobulin,
- thrombospondin,
factor V,
fibrinogen,
fibronectin,
platelet derived growth factor
high molecular weight
kininogen,
tissue plasminogen activator inhibitor-1
where is VWF found
- VWF from plasma or from granules
How does VWF react when it attaches to collagen
- Collagen exposed and the nature of the collagen allows the VWF to bind to it
- VWF binds to GPIb – intitial monolayer of platelets – subsequent activation, via a G-protein mechanism(facilitated by agonist relese ) – Shape change – disc to sphere – pseudopods – complex of Gpib IX, IIbIIIa, VWF, fibrinogen.
what are the agonist for VWF
– collagen, ADP, thrombin, adrenaline, serotnonin AA metabolites – TXA2
what acid does VWF release when it binds to IIb
arachidonic acid
describes what happens to the arachidonic acid released when VWF binds to IIb
- Arachidonic acid is released converted to by lipo-oxygenase enzymes to leucotrienes – chemoattractants to white cells, remaining Arachidonic Acid converted by cyclooxygenase and then TXA synthetase into Thrombocxane.
- Thromboxane causes further granule release and local vasoconstriction and further local aggregation – exerts this by intracellular calcium shifts.
what is another pathway by which VWF carries out its role
- 2nd pathway of activation by agonists interaction on membrane surface receptors and G protein activation of phopholipase C. – further calcium release – stimulate contractile system – liberation of Arachidonic Acid and further generation of TXA2
- Flip fop of membrane charge – negative charged moieties onto outer surface – procoagulant
name some serious inherited platelet disorders
- Lack GpIb – Bernard Soulier syndrome – have thrombocytopenia as well
- Lack GpIIb/IIIa – Glanzmann’s – all the clotting tests look normal except the fact that the platlets don’t work
- Likely to need platelets or Novoseven medication that is a turbo boost to the clotting system that try’s to get some thrombin activity
what is the disorder called when you lack Gp1b
– Bernard Soulier syndrome
What is the disorder called when you lack GpIIb/IIIa
Glanzmann’s – all the clotting tests look normal except the fact that the platlets don’t work
what are the less serious platelet conditions
- Storage pool disorders
* Weak agonist response defects
what is the most common inherited blood clotting disorder
von willebrand disease
what is the genetics of VW disease
• Autosomal inheritance – girls & boys
what are the types of VW disease
- Type 1 – mild to moderate deficiency
- Type 2 – protein present but defective
- Type 3 – total absent protein
