Haemostasis and thrombosis Flashcards
What is the purpose of the haemostatic system?
Creates a balance between clotting to stop a person from bleeding to death but not thrombosing to stop perfusion
What are von Willebrand factors (vWF)?
Giant adhesive plasma proteins that have many binding sites for:
-platelets
-collagen
-factor VIII
Usually assembled as multimers and rolled up in blood to hide binding sites but after collagen binds the shear stress of blood unravels them to expose binding sites
What are platelets?
Enucleated megakaryocyte fragments
Contain granules of vWF, fibrinogen and ADP
Adhesive surface receptors that can bind to vWF and collagen
How are platelets activated?
Stimulatory receptors can be activated by ADP, thromboxane and PGI₂
Changes shape to expose phospholipids, present proteins and release granule-s
Where are clotting factors synthesised and located?
Synthesised in liver with vWF in endothelium and FVIII in endothelial cells
Platelets in megakaryocytes
present in blood along regulatory proteins
What does platelet binding allow?
Binding to vWF via GP1b slows down and allows secondary collagen binding for activation
Can bind to other platelets using fibrinogen causnig Ca2+ influx and degranulation
TXA₂ produced from surface phosophollipids
What are the 3 main stages of haemostasis?
Vasoconstiction
Platelet plug formed - 1° haemostasis
Fibrin mesh stabilises platelet plug - 2° haemostasis
What are the steps involved in 1° haemostasis?
1) damaged endothelium means blood meets collagen/tissue factors
2) Rolled up vWF in blood binds to exposed collagen, causing unwinding and exposure of binding sites
3) vWF binds to glycoprotein 1b receptors on platelets, allowing 2° binding to collagen
4) Binding to vWF activates platelets
5) Platelets change shape and release alpha (vWF and fibrinogen) granules and dense (Serotonin ADP Ca2+) granules, present activated GPIIb/IIIa receptors
