Haemostasis Notes

Haemostasis

-Platelets play a central role in haemostasis- process that stops blood loss after blood vessel injury

Three components to Haemostasis

-Platelet activation to form a loose plug

-Local vasoconstriction to reduce blood flow to the affected area

-Activation of the coagulation cascade to convert soluable fibrinogen to fibrin strands that form a mesh around the platelet plug and trap other blood cells, to generate a more permanent repair

Vasoconstriction

-Damage to the endothelial cells leads to smooth muscle contraction, arterial contraction-lowers downstream blood pressure, key mediateors are serotonin, thrombaxane A2

i) Platelet activation

(Platelets are small cytoplasmic fragments of megakaroycytes, life span of 8-10 days in circulation-abundant in blood)

-injured endothelial cells release von Willebrand factor – these attach to the underlying collagen

-Glycoprotein 1B receptor on the platelet membranes bind to von Willebrand factor, other glycoprotein receptors bind to collagen

-This leads to platelet adhesion

-Stimulation of the glycoprotein receptors triggers the platelet activation pathway

-activation of glycoprotein receptor Ib activation of Phospholipase A2, forms arachidonic acid. Cyclo-oxygenase enzyme (inhibited by aspirin) converts arachidonic acid into Thromboxane A2- this is a platelet aggregator and vasoconstrictor

-Thromboxane A2 bind to receptors on the platelet membrane and lead to increase in internal calcium concentrations which leads to platelet activation, through rise in internal calcium concentrations

Rise in intracellular calcium:

-Release of granules:

Alpha granules: coagulation factors (Factor 5,8), fibrinogen, platelet derived growth factor

Delta/sigma granules: release serotonin (vasoconstrictor), ADP-binds to ADP receptors and increase internal calcium concentration, activation of the platelets and stimulates aggregation), calcium (binds the coagulation factors to phospholipid bilayer of platelets, binds coagulation factors together)

-Cogulation factors- have gamma carboxylated glutamate residues, vitamin K dependent process

-Thromboxane A2 and ADP promote platelet aggregation- primary platelet plug/ Haemostatic plug

-There is also an increase in intracellular calcium in activated platelets

-Change of shape: Psuedopodia emerge from normal smooth discoid plately surface, increase SA, increase adhesiveness of the platelets

-Glycoprotein 2b/2a exposure-these bind to fibrinogen and stabalise the platelet plugs

Coagulation

-There are two cascade pathways

intrinsic pathway coagulation is initiated automatically in a glass tube, due to the negative surfaces, activation of Factor 12

extrinsic pathway: Pathway is activated on...

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