Session 5 - Haemostasis

Question 1

What is clotting?

Answer 1

Clotting is the process whereby blood beocmes a sold mass when it makes contact with connective tissue.

Question 2

Describe the three steps of haemostasis

Answer 2

1. The severed artery contracts, not enough to stop the bleeding but enough to decrease the pressure downstream.
2. A primary haemostatic plug of activated platelets forms at the hole in the vessel sticking to the injured vessel and the connective tissue outside of it. It forms in seconds to minutes.
3. Secondary haemotatic plug forms as fibrin filaments stabilise the friable platelet plug into a blood clot. This occurs in around 30 minutes.

Question 3

What substances activate platelets?

Answer 3

1. Collagen surfaces
2. Thomboxane A2 (released by platelets)
3. ADP (released by platelets)
4. Thrombin

Question 4

Where is von Willebrand factor most commonly found?

Answer 4

On the subendothelial basement membrane.

Question 5

Through what mechanism does aspirin have anti-coagulant effects?

Answer 5

Aspirin will irreversibly inactivate cyclooxygenase which is one of the enzymes repsonsible for the production of thromboxane A2 and this in turn decreases platelet aggregation.

(Note: cyclooxygenase also produces prostaglandins which will increase sensitivity to pain and this is how they have an effect as a pain killer).

Question 6

Which substances that are part of the clotting cascade require vitamin K for their synthesis?

Answer 6

Factors 2, 7, 9 and 10.

Anticoagulants Protein C and protein S.

Question 7

What is the intrinsic pathway?

Answer 7

This is one of the pathways of the clotting cascade. It only requires factors that are contianed within the blood and is triggered by a negatively charged surface (including subendothelium or glass).

Question 8

What is the extrinsic pathway?

Answer 8

This is the pathway that is activated by components outside of the circulation. This is its name because it requires tissue factor (formerly known as factor III) which is present outside of the blood. This pathway is triggered by tissue factor released from damaged cells adjacent to the area of haemorrhage.

Question 9

What are the main natural anticoagulants?

Answer 9

• Protein C
• Protein S
• Antithrombin III

Question 10

What do platelets do in a clot as they are dying?

Answer 10

They cling to the fibrin and pull by their actin-myosin filmanets which pulls together the sides of small wounds. It also helps to squeeze out fluids.

Question 11

What happens in fibrinolysis?

Answer 11

1. Macrophages will enguld the fibrin and it is then destroyed by plasmin.
2. Plasmin is formed by the activation of plasminogen.
3. Plasminogen circulates freely in the blood and is activated by tissue plasminogen activator.

Question 12

Provide 3 examples of activators of plasminogen

Answer 12

1. tissue plasminogen activator (highest affinity for fibrin)
2. urokinase
3. Streptokinase (should only be used once as it is antigenic)

Question 13

What is a side effect of using plasminogen activators therapeutically?

Answer 13

Bleeding from the gums and nose most commonly.

In severe cases bleeding can also occur in the brain.

Question 14

What is an example of a fibrin degradation product? When would you see this elevated clinically?

Answer 14

D dimers. They are increased in conditions where there is thrombosis such as disseminated intravascular coagulation, deep vein thrombosis and pulmonary embolism.

Question 15

What is haemophilia A? Describe its inheritance and what it causes as a result.

Answer 15

An X-linked autosomal recessive disorder. This is where patients will get either a decresed amount or decreased activity of factor VIII.

30% of cases have no family history and occur as new mutations.

Question 16

What are the symptoms of haemophilia A?

Answer 16

• Easy bruising
• Massive haemorrhage after trauma and surgery
• Spontaneous haemorrhages occur in areas subject to minor trauma. eg. haemarthrosis

Question 17

What does APTT measure?

Answer 17

The intrinsic pathway.

Question 18

What does PT measure?

Answer 18

The extrinsic pathway.

Question 19

If a patient were to present with a normal platelet count, normal bleeding time, normal PT but a prolonged APTT what would this indicate?

Answer 19

This would indicate that the patient has a problem with an aspect of their intrinsic pathway of their clotting cascade. You would then go on to measure their factor VIII assay to look at the amount present in the patients blood. If low this confirms haemophilia A.

Question 20

What is haemophilia B? What will you see on their bloods?

Answer 20

Also known as christmas disease - it is a factor IX deficiency. It is an X linked recessive disease with variable clinical severity.

Their blood tests would show a normal platelet count, normal bleeding time, normal PT and prolonged APTT.

Question 21

How would you treat:

haemophilia A?

haemophilia B?

Answer 21

• Recombinant factor VIII
• Recombinant factor IX

RESPECTIVELY.

Question 22

What is Von Willebrand disease?

Answer 22

This is the most commonly inherited bleeding disorder. Patients can vary from being asymptomatic through to severe symptoms.

It is due to a deficiency or an abnormality in Von Willebrand Factor.

Question 23

What is the role of Von Willebrand Factor?

Therefore what would you see in a blood test of an individual with VWD in terms of their bleeding time, PT, and APTT?

Answer 23

• encourages aggregation of platelets at the subendothelial surface
• stabilises factor VIII protecting it from premature destruction.

A patient with VWD would therefore have a prolonged bleeding time, normal PT and a prolonged APTT due to potential defect in factor VIII function.

Question 24

A patient comes into the clinic and you see from their records that they have a low platelet count. What is the medical term for this and what would you expect to see from their bleeding time, PT and APTT?

Answer 24

The medical term is thrombocytopenia

You would expect to see a prolonged bleeding time but a regular PT and APTT.

Question 25

What are 4 reasons for thrombocytopenia occuring?

Answer 25

• Decreased production of platelets
• Decreased platelet survival - eg. immunological destruction
• Sequestration - splenomegaly
• Dilutional - due to massive blood transfusions.

Question 26

Provide some examples of why DIC would occur?

Answer 26

• Sepsis - especially when gram negative bacteria produce an endotoxin which activates clotting
• Severe trauma
• Burns
• Complications of childbirth - eg. amniotic fluid embolism
• malignancy
• snake bite

Question 27

How would you treat DIC is bleeding was an issue?

What would you do if you were beginning to see organ failure?

Answer 27

If bleeding was an issue: administer fresh frozen plasma, platelets, cryoprecipitates (which contain factor VIII, fibrinogen, WVF and factor XIII), and red blood cells may be required

If you are starting to see organ failure you could have extensive ischaemia as a result of the microthrombi and therefore you would administer heparin to the patient.

Question 28

What important blood test could you take to diagnose DIC?

Answer 28

D-dimers. These are a fibrin degradation product that are released in large numbers in DIC.

Question 29

What is thrombophilia? Provide clinical examples.

Answer 29

An inherited or acquired defect of haemostasis resulting in a predisposition to thrombosis.

Clinical examples: antithrombin deficiency, protein C or protein S deficiency and antiphospholipid syndrome.