haemostasis and thrombosis Flashcards
haemostatic mechanisms: summarise normal haemostatic mechanisms
define haemostatic system
balance between clotting to stop bleeding to death, and not thrombosing to stop perfusion
blood components involved in haemostasis
plasma, coagulation factos, regulatory proteins
factors and cofactors involved in haemostasis
vWF, platelets, pro-coagulant proteins (e.g. VIIa)
what triggers cogagulation from outside circulation
collagen, tissue factor
what is von Willebrand Factor (vWF)
giant adhesive plasma proteins that have many binding sites for platelets, collagen and factor VIII
structure of vWF
assembled to multimers and rolled up in blood to hide binding sites
what happens to vWF upon collagen binding
shear stress of blood causes it to unravel and become long and thin, exposing binding sites
what are platelets
enucleated fragments of megakaryocyte containing granules of vWF, fibrinogen and ADP
structure of platelets
possess adhesive surface receptors that can bind to vWF and collagen; stimulatory receptors can be activated by ADP (purine receptors), thromboxane and PGI2
platelets upon activation
changes shape to expose phospholipids, present proteins and release granules
how do platelets bind to vWF and why
via GP1b to slowdown and allow secondary collagen binding for activation
how can platelets bind to other platelets and what is the outcome
by fibrinogen, causing Ca2+ influx and degranulation
what is produced in platetets using phospholipids from the surface
thromboxane A2
where are clotting factors mostly synthesised
liver
where is vWF and clotting factor VIII synthesised
endothelium
3 stages of haemostasis
vasoconstriction (due to endothelin and neural activity), primary (platelet plug formation), secondary (fibrin mesh stabilises platelet plug)
what is primary haemostasis sufficient for
small vessels
formation of platelet plug
endothelium damaged, causing blood to meet collagen/tissue factors → rolled up vWF binds to exposed collagen → stretches and exposes platelet binding sites → vWF binds to GP1b receptors on platelets → platelets change shape and release alpha granules (fibrinogen and vWF), dense granules (serotonin, ADP and Ca2+) → platelets present activated GPIIb/IIIa receptors → vWF released enables more platelets to be captured, while fibrinogen allows platelets to stick together using GPIIb/IIIa
what is a fibrin mesh required for
larger vessels, stabilise platelet plugs
formation of fibrin mesh
endothelium damaged, causing blood to meet collagen/tissue factors → circulating FVIIa binds to newly exposed tissue factors → complex forms that converts FIX to FIXa and FX to FXa → TFPI binds to FVIIa, FIXa and FXa to stop, but if stimulus large enough FXa converts FII to thrombin → thrombin activates FVIII and FV → make complexes with Ca2+, phospholipids, FIXa and FXa → FIXa converts FX to FXa → FXa converts FII to thrombin → levels of thrombin increase rapidly in thrombin burst, cleaving fibrinogen to insoluble fibrin that forms a mesh
why is a fibrin mesh stronger
FXIII activated by thrombin forms fibrin cross links that are more resistant to fibrinolysis
