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L5 Haemostasis I
Cytoskeleton plays key role
1
...
Elongation of
pseudopodia into
proplatelet
extensions
(microtubules
become more highly
organised)
3
...
Delivery of platelet material to tips
5
...

 Granules move backwards and forwards
 Delivery of vesicles, proteins and organelles to newly forming platelets occurs via kinesins and microtubule
tracks
(Pro)platelets formation and release in vivo
 In vivo, the process may not be explosive as in vitro, as it requires the proplatelets to cross the barriers of the
blood vessel wall
 This initials contact with and protrusion through the blood vessel wall requires the formation of actin rich
podosomes and matrix metalloprotease activity
...
The clots then are cleared
 Pathological thrombus formation can give rise to chronic thrombosis which can occlude blood vessels and cause
downstream tissue ischaemia (Heart attacks, Stroke, DVT)
 Resting platelets have
o No nucleus
o An average lifespan of about 8-10 days
o Are small 3-5μm
o Membrane network – open canalicular system; dense tubular network
o Organelles – including granules, mitochondrion
o Plasma membrane and surface glycocalyx
o Cytoskeleton – actin, tubulin and spectrin

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Upon activation platelets (are important for haemostatic function)
o Change shape
o Secrete granules
o Become sticky
The resting platelet cytoskeleton – membrane skeleton
o Spectrin interconnects with F-actin filaments forming a network under the plasma membrane – a single
continuous network of actin and spectrin
o The network helps the platelet maintain integrity when subjected to the shear forces of blood flow
o Microtubules are organised into a coil around the end of the discoid shape – platelet marginal band
 This coil is made up of 1 long stable microtubule and 6-8 short dynamic microtubules
 The microtubules coil expands, helping to drive rounding of the platelet before coiling in to a
central small coil as the platelet spreads
 Microtubules ultimately depolymerise and can be reformed to support the spread platelet shape
The resting platelet cytoskeleton – actin skeleton
o These filaments are held together in a network by filamin, α-actinin and via spectrin/adducin
o Actin cytoskeleton is also linked to receptors
o Along with spectrin, provides a support for maintenance of platelets integrity in flow
Platelet Activation
1
...
Turnover of the resting actin
cytoskeleton
3
...
Polymerisation of actin and MTs spreading

Platelet spreading is driven by actin polymerisation
and organisation
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Platelets contain 2 types of granules
o α granules (bigger)
o Dense granules
o Also contain 0-2 lysosome which can
secrete hydrolases
Granules need to be brought close to the plasma
membrane and the membranes need to fuse to allow
content release
Granule release is mediated by SNARE proteins
o SNAREs – a family of proteins that mediate
vesicle fusion with the membrane
o v-SNARE – vesicular SNAREs
o t-SNAREs – target SNAREs on plasma
membrane
How do platelets become sticky
o Adhesion is mediation by the activated of
cell adhesion molecules – integrins
o Agonists binding to receptors triggers
activation of the integrins
Platelet activation via multiple surface receptors
Secretion of granules many different
compounds/proteins which have wide ranging
effects on platelet, endothelial cells, leucocytes
and coagulation

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Platelet activation leads to the activation of integrins which form cross bridges between platelets forming the
platelet aggregate



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