haemostasis and thrombosis: which are the triggering factors?
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Course
Mechanism of disease
Institution
The University Of York (UOY)
The document focuses on the process of haemostasis, describing it and the steps that characterise it. It then describes the process of thrombosis: why does it happens and the main factors that cause it. It then explains Myocardial infarction and reperfusion injury.
It offers an in depth overview ...
HAEMOSTASIS AND THROMBOSIS
Haemostasis = in a physiological state it means maintaining blood flow within vasculature. On a vessel
injury/trauma, it relates to limit or arrest bleeding by forming a cot at the site of injury while maintaining
blood flow in the rest of the vessel. Finally, it involves the removal of the blood clot after wound
healing.
Thrombosis= it’s the pathological manifestation of haemostasis: when u start getting clot when they
are not necessary causing restriction and blockage of blood vessel, causing hypoxia and tissue
damage. Thrombi can also dislodge leading to embolisation.
In the photo= lumen of a mouse blood vessel.
4 STAGES OF HAEMOSTASIS
1. First stage = VASCULAR SPASM= damaged blood vessel constrict (followed released of some
neurotransmitters) Reducing blood flow in the damaged area ( watch video).
2. Second stage = PLATELET PLUG FORMATION= 1^ haemostasis= Platelets bind to the damaged
vessel wall and form a platelet plug
3. Third stage= Coagulation / secondary HAEMOSTASIS = stable clot forms by converting fibrinogen
to fibrin
4. Fourth stage = FIBRINOLYSIS= safely breaking down a clot after the vessel has been repaired
WHAT ARE PLATELETS ?
Small fragments of megakaryocyte cytoplasm. An adult
produces around 10^11 platelets/day. The physiological
range is 150-400 x 10^9/L of blood. They circulate in the
blood and have a lifespan of 5/9 days. Old platelets are
destroyed by KUpfer cells in the liver or by phagocytes in
the spleen.
Because they don’t have nucleus they can’t make new
proteins so they contain all the factors required for their
functions. They contain membrane proteins to stick to
stuff, they also have secretory granules: they are
released in order to activate the secondary haemostasis.
SCOCS, surface-connected open cannalicular
system= the granules are moved from this scocs to
spread all over the vessel
There are Two types of granules
Alpha granules: most prominent and numerous (50-80/ platelets). Alpha granules contain:
adhesive proteins = fibrinogen, fibrinectin, vWF
Platelet-specific proteins = PF4, PDGF
Membrane proteins = GPIIaIIIb, GPIb/IX/V
Alpha granule- specific proteins =P-selectin; it’s also used to indicate the activation of the
granules.
, Dense granules: usually present as 2-7 per platelet. They are referrred to be dense because they are
electron dense when they stained with osmium tetroxide. Dense granules contain:
Vasoconstriction agents =serotonin which helps the blood vessel to shrink and to avoid blood loss
from the vessel
Platelet agonists = ADP, ATP
Calcium -promotes integrin activation - and magnesium
PLATELET MEMBRANE RECEPTORS
1. Platelet adhesion
Following vessel damage, endothelial cells of the vessel are damaged. They exposed the sub
endothelial layers which contains many proteins to which planets adhere to, in particular to collagen-
associated. The platelet is now "tethered" to the sub-endothelium. Shear stress is a critical component
of tethering.
Blood flow then "rolls" the platelet along the sub-endothelium promoting more GPIb/vWF
associations, and creating firmer adhesion between the platelet and the sub-endothelium
This firmer adhesion allows initiates platelet activation, resulting in granule release (which contain
platelet agonist) and conformation changes in specific adhesion molecules, leading to strong adhesion,
shape change and further activation. The newly platests can now start to interact with the already
activated one
2. Platelet plug formation
A platelet monolayer forms on the exposed sub-endothelial layer. The activated platelet monolayer
release granules containing platelet agonists such as ADP, thromboxane A, and adhesive proteins,
such as fibrinogen, which recruits further platelets to the developing plug.
As the newly-recruited platelets are attracted to the plug, they also change shape, allowing for greater
platelet-platelet interactions, especially via fibrinogen cross-bridges, which bind to GPilalllb
Platelets integrin allbß3 (also known as GPIlb Illa and CD41/61)
• =is a membrane localised glycoprotein expressed almost exclusively by platelets and
megakaryocytes
• It's primary role is to act as a receptor for fibrinogen and von Willebrand factor to aid platelet
activation
• In addition to binding extracellular matrix, integrins are able to signal into the cell to alter its function
• However, as allbß3 is so essential for platelet function and its activity potently drives platelet
activation, it must be maintained in an inactivate state until required.(mouse models without integrin
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