Haemostasis - Platelets Lecture 5

Question 1

Describe the structure of a resting platelet

Answer 1

Small 3-5nm biconvex disc

No nucleus

Contain open canalicular system

Organelles including granules and mitochondria

Has surface glycocalyx

Has an actin, tubulin and spectrin cytoskeleton- actin supports edges, tubulin supports middle and spectrin lays under the PM and chord the actin cytoskeleton

Question 2

How do platelets change upon activation?

Answer 2

Resting Platelet cytoskeleton =spectrin interconnects with F-actin filaments forming a network under the plasma membrane - a netword of actin and spectrin. The filaments are held together by filamin, alpha-actinin via spectrin/adducin. (helps maintain platelet intergrity during flow). Microtubles are organised in a coil around the end of the discoid shape- platelet marginal band.

When acitviated, Change shape- relaxation of membrane skeleton➡️ turnover of the resting actin cytoskeleton➡️ changes in the microtubule cytoskeleton➡️ polymerisation of actin and MTs

Platelet spreading - microtuble coil expands and depolymerise and cam be reformed to spread platelet shape allowing it to spread.

Secrete granules- secrete alpha and dense granules (mediated by t-SNAREs and v-SNAREs)

• Alpha granules contain integral proteins, coagulants, adhesion proteins (fibrinogen vWB), chemokines, growth factors, angiogenic factors, immune mediators
• Dense granules contain cations, polyphosphates, bio active amines (serotonin and histamine) nucleotides (ADP, ATP)

Become sticky- adhesion is mediated by integrines, ligand binding activated membrane bound integrines which are joined by fibrinogen. When agonist binds to receptor and platelet is activated, a signalling cascade activates, taking intgrins and folds it to become active. THe intergrin binds to other integrins which binds to other platelets.

Question 3

How are granules secreted

Answer 3

Need to be bought close to the plasma membrane and need to fuse to allow content release.

Regulated by SNARE protiends.

V-Snare are vesicle snares

t-SNAREs on plasma membrane

WHen granule comes close to membrane, V-SNAREs and t-SNAREs react which brings the granule close to the plasma membrane where the granule secretes contents.

Question 4

List done common platelet receptors and their ligands

Answer 4

GP1b-9-5 complex bins to vWF (von wilibran factor which can activate platelets when it detects damage in vessel wall)

GP6/FcRy complex binds collagen (signals cause granules to be secreted using SNARE proteins and release TXA2 and ADP which are important secondary activators in platelets)(laminin, convulixin)

Alpha2beta1 integrin also binds collagen (laminin)

TxA2- thromboxane

P2Y1, P2Y12- ADP

PAR1, PAR4- thrombin

Thromboxane, ADP, thrombrin bind to platelet to further support activation and can also activate other platelets as they arrive to site of damage.

Alpha2b-beta3 integrin is activated by all the other factors which then binds fibrinogen allowing it to stick to other cells to increase surface area and block the wound.

Question 5

What happens to platelets if the vessel wall is damaged?

Answer 5

Usually the platelets receive inhibitory signals from the intact vessel wall

Damage cause the release of PGI and the exposure of collagen and vWB

Platelets roll across surface become adhered and start to spread, secrete TX(A2) and ADP to recruit more platelets which aggregate by fibrinogen becoming fibrin and forming a mesh around the plates forming as thrombus on the site of damage