Haemostasis

Question 1

What is haemostasis?

Answer 1

The arrest of bleeding and maintenance of vascular patency

Question 2

What are the 4 components of normal haemostasis?

Answer 2

Platelet plug, fibrin clot, fibrinolysis, naturally occurring anti-coagulants

Question 3

What happens in primary haemostasis? When is this required?

Answer 3

Formation of a platelet plug - needed in all bleeds

Question 4

What happens in secondary haemostasis? When is this required?

Answer 4

Formation of a fibrin clot - required in more severe bleeds

Question 5

What is fibrinolysis?

Answer 5

The breaking down of the fibrin clot from the edges, to prevent vascular occlusion

Question 6

Where are platelets formed? What from?

Answer 6

Formed in the bone marrow by ‘budding’ from megakaryocytes

Question 7

Are platelets nucleated? What is their lifespan?

Answer 7

No / 7-10 days

Question 8

What are the two phases of primary haemostasis?

Answer 8

Platelet adhesion and platelet aggregation

Question 9

How does platelet adhesion in primary haemostasis occur?

Answer 9

When there is endothelial damage, this exposes collagen which platelets stick to. VWF and other proteins are also released which platelets have receptor for.

Question 10

How does platelet aggregation in primary haemostasis occur?

Answer 10

Platelets secrete various chemicals which leads to aggregation

Question 11

Where is Von-Willebrand factor released from?

Answer 11

Endothelial cells, and also the platelets themselves

Question 12

What is the vascular cause of failure of formation of the platelet plug?

Answer 12

As we get older, our vessels contain less collagen

Question 13

The platelet plug can fail to form as a result of an a) reduced number and b) reduced function of platelets. Give a reason for each?

Answer 13

a) Immune thrombocytopenic purpura b) Anti-platelet drugs or NSAIDs

Question 14

The platelet plug can fail to form as a result of a deficiency of VWF - what is the most common cause for this?

Answer 14

Inherited disorder

Question 15

What are some consequences of failed formation of the platelet plug?

Answer 15

Spontaneous bruising and purpura / mucosal bleeding / intracranial haemorrhage / retinal haemorrhage

Question 16

What are some examples of mucosal bleeds which may occur with primary haemostasis failure?

Answer 16

Epistaxis, GI bleeds, conjunctival bleeds, menorrhagia

Question 17

What is the screening test for primary haemostasis?

Answer 17

Platelet count

Question 18

Describe the role of platelets in the formation of a fibrin clot?

Answer 18

Their surface is usually negatively charged (to repel - clotting factors). However, when haemostasis is required they secrete Ca++ which then sits on the surface to make them positively charged (to attract - clotting factors)

Question 19

Clotting factors are enzymes. What happens when they are all brought together at the platelet plug?

Answer 19

They all start to activate each other

Question 20

When the endothelium is damaged, what things are released to essentially initiate secondary haemostasis?

Answer 20

Tissue factor, which activates factor VII

Question 21

What are the roles of tissue factor and factor VII in secondary haemostasis?

Answer 21

To activate factors V and X

Question 22

What are the roles of factors V and X in secondary haemostasis?

Answer 22

To activate prothrombin (factor II) which gets activated to thrombin

Question 23

In secondary haemostasis, thrombin (factor II) generates what? From what?

Answer 23

Fibrin (factor I) / fibrinogen

Question 24

When thrombin is first generated in secondary haemostasis, what does it do?

Answer 24

It activates factors VIII and IX (important) and factors XI and XII (not so important) which then amplify the whole process by producing more factor V and X to produce more thrombin

Question 25

How do a) single and b) multiple clotting factor deficiencies come about? Give examples of each.

Answer 25

a) usually inherited e.g. haemophilia b) usually acquired e.g. disseminated intravascular coagulation

Question 26

What is the screening test used to measure initiation in secondary haemostasis (i.e. production of TF and factor VII)?

Answer 26

Prothrombin time

Question 27

What is the screening test used to measure amplification in secondary haemostasis (i.e. production of factors VIII and IX)?

Answer 27

Activated partial thromboplastin time

Question 28

What needs to happen to plasmin before it can be used to degrade fibrin in fibrinolysis?

Answer 28

Needs to be converted from plasminogen by tPA

Question 29

What is the role of plasmin in fibrinolysis?

Answer 29

Converts fibrin to fibrin degradation products (D-dimers)

Question 30

What are some naturally occurring anti-coagulants?

Answer 30

Serine protease inhibitors (anti-thrombin III) and protein S/C

Question 31

What is the role of anti-thrombin III?

Answer 31

Turns of thrombin and also some clotting factors directly

Question 32

What is the role of protein C/S?

Answer 32

Turns off factors V and VIII

Question 33

When thrombin recognises that haemostasis has been achieved, what does it do?

Answer 33

Binds to thrombomodulin which switches it from activating clotting factors to activating protein C

Question 34

What is a thrombophilia?

Answer 34

A deficiency of naturally occurring anti-coagulants