Platelets

Question 1

What is the life span of a platelet? Describe platelets?

Answer 1

Small annucleated
Normal platelet count 150-350
10 days

Question 2

Describe how the megakaryocyte looks on the blood film

Answer 2

Large - 10 regular cells
has nuclear lobes
and heavily granulated cytoplasm

Question 3

what are the platelet functions?

Answer 3

They form the primary platelet plug
They act as a surface for coagulation factors
They are important in promoting endothelial repair
Produce finbrinogen, FV vwf

Question 4

How do platelets slow down to clot?

Answer 4

They bind weakly with the A1 domain of vwf via Glp1b at damaged endothelium - this is rapid on/off binding which slows down the platelet

Question 5

After slowing of the platelet, where does it bind?

Answer 5

It binds to collagen via GPVI and Glp1a2a at the damaged surface this activates them

Question 6

What happens to activated platelets?

Answer 6

They recruit more platelets and degranulate releasing ADP and thromboxane A2

Question 7

What happens to ADP?

Answer 7

It binds the P2Y12 receptor

Question 8

What happens to thromboxane?

Answer 8

It recruits more platelets as it causes activated platelets to express Glp2b3a receptors

Question 9

Where does the platelet bind via Glp2b3a?

Answer 9

It binds to the c4 domain of vwf causing platelet adhesion.

Question 10

What is primary haemostasis?

Answer 10

Formation of an unstable platelet plug, platelets adhesion and aggregation

Question 11

Where are platelets stored?

Answer 11

They are stored in the spleen

Question 12

How are the platelets released?

Answer 12

2 thoughts: shear forces forces the platelets from bone marrow out
or into the lungs and microvasculature which leads to release of platelets from the megakaryocytes

Question 13

What are the 2 types of granules?

Answer 13

ADP and dense granules

Question 14

What is found on the surface of the platelts

Answer 14

Important receptors
A2b3 - Platelet platlet binding
P2y12 - adp
Par - thromboxane

Question 15

Describe platelet cytoskeleton

Answer 15

from rest -> more round -> more spread platelet is activeated
Microtubules maintain discoid shape
and actin myosin filaments lead to movement

Question 16

How do platelets bind to vwf what is the bidning site?

Answer 16

gp1ba

Question 17

How does the platelet bind to the collagen directly?

Answer 17

glp6

glp1a2a

Question 18

What is released when there is activation of platelet? What happens?

Answer 18

Increase release of adp and thromboxan

activating glpa2b3 which then binds fibrinogen leading to growth of haemostatic plug

Question 19

WHat is the importance of the platelet activation?

Answer 19

Exposures phosphatidylserine to act as a site for coagulation to occur

Question 20

At what level is spontaneous bleeding a possibility?

Answer 20

<40

Question 21

What receptor is affected in glanzmann thrombasthenia?

Answer 21

glpa2b3
Platelets are unable to aggregate normally
bleeding patterns are variable
but it is a rare disease

Question 22

What is the problem with bernard soulier syndrome?

Answer 22

GP1Ba
GP1bB and GPIX
THrombocytopenia
these platelets are not able to adhere properly from the start
Giant platlets result

Question 23

WHat is the platelet form VWD?

Answer 23

Increased in binding of vwf and platelets this is a gain of function due to mutation in Glp1ba

Question 24

What is grey platelet syndrome?

Answer 24

mutation in NBEAL2 - mild .moderate bleeding syndrome, problem with trafficking

Question 25

How do platelets bind to collagen?

Answer 25

Platelets bind via gpiba complex with vwf in rapid on rapid off binding, slowing it down so it can bind via its other receptors a2b1 and GPVI complex to collagen

Question 26

What happens after binding?

Answer 26

Trigger intrcellular signalling via plc gamma which leads to calcium entry leading to exposure of a2b3 binding site which then bridges another platelets with fibrinogen

Question 27

What happens once fibrinogen is bound?

Answer 27

THis further stimulates the cells to influx calcium to have more activation of the cells and exposure of a2b3. There is also production of thromboxane and ADP release which binds to each of their own receptors on the platelet.

Question 28

How are platelts able to act as the surface for coagulation?

Answer 28

Scramblase from the platelets switched the symmetry of the membrane and lead to exposure of PS on the outside which allows for coagulation factors to bind and generate thrombin

Question 29

What is the role of the endothelium in activation/inhibition of platelets?

Answer 29

THe endothelium produces nitric oxide and prostacyclin which act to increase cAMP and this inhibits platelet function, there is also adp-atp production which also leads to cAMP release

Question 30

What are the intrinsic regulators that platelets have?

Answer 30

They have receptors like PECAM, CEACAM, JAM-A and ESAM which act as intrinsic regulators and inhibitors of platelet activity

Question 31

Where is thromboxane and prostacyclin made?

Answer 31

Thromboxane - platelet
Prostacyclin - endothelial cells
both made from arachidonic acid
PGI2 is a potent inhibitor of platelet function, thromboxane is a potent inducer of platelet aggregation

Question 32

Mechanism of Clopidogrel?

Answer 32

inhibits ADP binding to the p2y12 receptor so prevents activation of platelets