Week 3- bleeding disorders

Question 1

What are some causes of vascular abnormalities that could lead to a disorder of primary haemostasis?

Answer 1

Marfans syndrome- collagen is affected so they get excessive bruising, bleeding and floppy heart valves

Vasculitis- inflammation- usually autoantibodies attack vessels making them leaky

Old age- you lose collagen as you grow older.

Steroids- Can lead to thinning of the skin and vessel wall injury by reducing collagen.

Question 2

Someone suffering from henloch schonlein purpura will have what symptoms?

Answer 2

They will have mucosal and GI bleeds.

Question 3

What does thrombocytopenia mean?

Answer 3

Low platelets.

Question 4

Is thrombocytopenia a hereditary or acquired disease?

Answer 4

Hereditary thrombocytopenia Is extremely rare.

Acquired is much more common.

Question 5

What are the two broad reasons for acquired thrombocytopenia?

Answer 5

Reduced production-bone marrow problem

Increased destruction

Question 6

What are the causes of peripheral platelet destruction?

Answer 6

Coagulopathy- e.g. DIC
Autoimmune- immune thrombocytopenic purpura (ITP)
Hypersplenism- anything that causes the spleen to be enlarged e.g. portal hypertension.

Question 7

Describe what occurs in ITP?

Answer 7

Autoantibodies stick to the platelets and cause them to be removed by the reticuloendothelial system.
The bone marrow makes lots and lots of platelets but they are killed, leaving the patient thrombocytopenic.

Question 8

What can cause functional defects in platelets?

Answer 8

Drugs e.g. aspirin, NSAIDs. Stop the platelets sticking together.
Renal failure- a build up of toxins can interfere with platelet function.

Question 9

Is VWF deficiency hereditary or acquired?

Answer 9

Hereditary is much more common than acquired.

Question 10

How is VWF deficiency inherited?

Who does it affect?

Answer 10

Autosomal dominantly.

Affects both men and women equally, however tends to be seen more in women because of heavy periods.

Question 11

What type of haemostasis does VWF deficiency affect?

Answer 11

Mainly primary however also affects secondary. VWF carries around factor VIII so without it you will also have a factor VIII deficiency.

Question 12

What symptoms will be seen with VWF deficiency?

Answer 12

Mucosal bleeding
Purpura (bruising)
Menorrhagia in women.

Question 13

What can failure of the fibrin clot forming be due to?

Answer 13

Single clotting factor deficiency
Or
Multiple clotting factor deficiencies.

Question 14

What are some causes of single clotting factor deficiencies?

Answer 14

Generally hereditary causes e.g. haemophilia.

Question 15

What are some causes of multiple clotting factor deficiencies?

Answer 15

These are generally acquired e.g.
DIC
Liver failure- all the clotting factors are produced here so without this you can’t make them
Vitamin K deficiency/warfarin therapy- to get the negative charge on the clotting factors to be attracted to the platelets, you need vitamin K.

Question 16

What investigations are done into vitamin K deficiency and what are their results?

Answer 16

Do APTT and PT.
Both will be prolonged as the clotting factors are not attracted to the platelet plug. Tends to be more sensitive to factor VII so PT may be prolonged more.

Question 17

Where are coagulation factors synthesised?

Answer 17

In liver hepatocytes.

Question 18

Which factors are carboxylated by vitamin K?

Answer 18

10, 9, 7, 2.

Question 19

How does vitamin K get into the body?

Answer 19

Brought in by our diet and also synthesised by the intestine.

Question 20

Where is vitamin K absorbed?

Answer 20

Absorbed in the upper intestine.

Question 21

What is needed for vitamin K absorption?

Answer 21

Bile salts (therefore gall bladder has to be working properly).

Question 22

What are some causes of vitamin K deficiency?

Answer 22

Poor dietary intake (present in leafy green veg).
Malabsorption
Obstructive jaundice- Bile salts are not getting into the bowel.
Vitamin K antagonists (warfarin)
Haemorrhagic disease of the newborn- lack of vitamin K at birth.

Question 23

What is disseminated intravascular coagulation?

Answer 23

Excessive and inappropriate activation of the haemostatic system.
You get microvascular thrombus formation, which can lead to end organ failure.
Also clotting factor consumption leading to bruising, purpura and generalised bleeding.

Question 24

Which test is likely to show failure of multiple clotting factors first?

Answer 24

Likely to be prothrombin time as this one contains factor VII. Factor VII has a half life of about 7 hours whereas the others have a half life of about 3 days.

Question 25

How can you distinguish between DIC and liver failure causing the multiple clotting factor deficiencies?

Answer 25

In DIC- the D dimers will be greatly increased as massive fibrinolysis is occurring. Whereas in liver failure they may be raised but not a lot.

Question 26

What can cause DIC?

Answer 26

Sepsis
Obstetric emergencies (placenta is very rich in tissue factor so if it infarcts, massive amounts of this are released into the mothers circulation)
Malignancy
Hypovolaemic shock- lack of oxygen leading to mass tissue damage.

Question 27

How do you treat DIC?

Answer 27

Treat the underlying cause
Replacement therapy- replace platelets, replace fibrinogen (cryoprecipitate), plasma transfusions (this will only maintain their state, you need to treat the underlying cause for them to become better).

Question 28

What is haemophilia?

Answer 28

An X linked hereditary disorder in which abnormally prolonged bleeding recurs episodically at one or a few sites on each occasion.

Question 29

What is haemophilia A?

Answer 29

A factor VIII clotting deficiency.

Question 30

What is haemophilia B?

Answer 30

A factor IX clotting deficiency.

Question 31

Which is the more common haemophillia?

Answer 31

Factor VIII (A) is far more common than haemophilia B.

Question 32

Will people with haemophilia suffer with nose bleeds, paper cuts bleeding excessively?

Answer 32

No- there is no issue with primary haemostasis. You will only get bleeding from medium-large blood vessels.

Question 33

What will be shown in PT and APTT tests with haemophilia?

Answer 33

PT will be normal

However they will have a prolonged APTT.

Question 34

What are the clinical features of haemophilia A and B?

Answer 34

Recurrent haemarthroses (bleeding into joints and muscles)
Recurrent soft tissue bleeds
Prolonged bleeding after surgery, dental extractions and invasive procedures.

Question 35

Which joints tend to be bled into in haemophilia?

Answer 35

Ankle, knee, elbow (weight bearing joints)

Question 36

What occurs in the joint once there has been a bleed?

Answer 36

The bleeding irritates the synovium, leading to formation of new blood vessels (neovascularisation). This blood vessels formed are leaky and more prone to bleeding.
After recurrent bleeding you get fusion of joints.

Question 37

In children, what treatment can be offered for haemophilia?

Answer 37

Factor VIII replacement.