L04-Platelets and coagulation

Question 1

What does the term clot refer to?

Answer 1

An intravascular thrombus

Question 2

What does a haemostasic response involve normally?

Answer 2

Complex interactions between activated plasma clotting factors and platelets at the site of injury.

Question 3

How are platelets produced?

Answer 3

They are produced by megakaryocytes in the bone marrow

Question 4

What is the normal lifespan of a platelet?

Answer 4

8-12 days

Question 5

What is the initial response to damaged endothelium?

Answer 5

Transient local vasoconstriction in order to reduce blood loss

Question 6

What is the structure of a clot surrounding damaged endothelial tissue?

Answer 6

The inner shell consists of a dense inner core made up of fully activated platelets
This is surrounded by an outer shell of partially activated loosely packed platelets

Question 7

What are the three main types of granules contained within platelets?

Answer 7

Dense granules - contain mediators of platelet activation such as serotonin, adp and calcium
Alpha granules - contain a number of clotting factors including FV, FVIII, fibrinogen, von Willebrand factor
Glycogen granules - provide the energy source for platelet reactions

Question 8

Which are the two most important platelet glycoprotein receptors and what do they do?

Answer 8

GP1b - attaches to von Willebrand factor to form the initial tethering of the platelets
GPIIb/IIIa - is activated after tethering and expresses vWF which causes further platelets to tether and begins to form the clot

Question 9

What are the inhibitors of coagulation?

Answer 9

Tissue factor pathway inhibitor (TFPI)
Antithrombin
Protein C
Protein S

Question 10

What are two platelet inhibitors?

Answer 10

Prostacyclin

Nitric oxide

Question 11

What initially activates platelets at damaged endothelium?

Answer 11

ADP released from damaged blood vessel endothelial cells. Along with exposed collagen and thrombin

Question 12

How are blood coagulation factors synthesised and released?

Answer 12

They are synthesised in the liver and released into the circulation in inactive precursor forms

Question 13

What vitamin is required for synthesising some of growth factors and which growth factors are these?

Answer 13

Vitamin K is required to synthesise prothrombin (factor II) F VII, IX and X
This is why it is given to all babies in hospitals as a deficiency can lead to bleeding tendencies

Question 14

Which factors are cofactors in the coagulation cascade and for which factors?

Answer 14

FV is a cofactor for activated FX

FVIII is a cofactor for activated FIX

Question 15

What is the result of ADP activating platelet metabolic pathways?

Answer 15

the release of dense and alpha granules which consolidates the platelet responce

Question 16

What is von willebrand factors use other than for platelet adhesion?

Answer 16

It is a natural carrier of factor VIII

Question 17

Where is von willebrand factor sythesised?

Answer 17

It is synthesised in blood vessel endothelial cells and megakaryocytes

Question 18

Which factor initiates the cooagulation cascade and how does it go about doing this?

Answer 18

FVII initiates the cascade by becoming activated by binding to tissue factor which is exposed on damaged membranes.

Question 19

What is the action of activated FVII?

Answer 19

It directly activates FX which with the help of FV converts prothrombin into thrombin

Question 20

The thrombin formed by FXa is not generated in enough quantity to cause significant fibrinogen to fibrin conversion, what does the thrombin do instead?

Answer 20

It releases FVIII from vWF and activates it along with activating FXI and FV.

Question 21

What is the final stage of the coagulation cascade?

Answer 21

Activated factors VII and XI generated activated FIX which with the aid of its cofactor FVIII it activates FX which generates sufficient thrombin to generate a clot.

Question 22

After the initiation of coagulation which part of the cascade is inhibited?

Answer 22

the direct activation of FX by FVIIa which is inhibited by extrinsic pathway inhibitor (EPI)

Question 23

What is bernard-soulier syndrome?

Answer 23

Deficiency of membrane GPIb

Question 24

What is haemophillia A?

Answer 24

Deficiency of FVIII

Question 25

What is Glanzmann’s Thrombasthenia?

Answer 25

Deficiency of GPIIb/IIIa

Question 26

What is haemophilia B?

Answer 26

FIX deficiency

Question 27

What is fibrinolysis and what enzyme does it involve?

Answer 27

It is the breakdown of the fibrin clot once the bleeding has stopped. It involves the enzyme plasmin.

Question 28

What is the role of tissue plasminogen activator (tPA)?

Answer 28

It is incorperated into the fibrin clot as it forms in order to allow attachment and conversion of plasminogen to plasmin when the clot needs to be broken down.

Question 29

How does protein C prevent formation of clots at sites other than that of the injury?

Answer 29

Thrombin cleaves protein c into its active form which with its co-factor protein s enzymatically cleaves activated FV and FVIII circulating in the blood

Question 30

What is hereditary thrombophilia?

Answer 30

Most prevalent is a mutation in factor V that results in impaired protein c activity.
Other common thrombophilias are deficiencies of protein C, S or antithrombin.

Question 31

What is prothrombin time and what does it tell you?

Answer 31

It measures the time for the extrinsic and common clotting pathways. An isolated prolongation indicates an FVII deficiency.

Question 32

What is activated partial thromboplastin time?

Answer 32

It measures the time for the intrinsic and common clotting pathways. An isolation prolongation requires further tests to see if it is a deficiency or an inhibitor?

Question 33

What do prolonged PT and APTT show?

Answer 33

There is a single factor deficiency in the common pathway or multiple factor deficiencies