HAEMOSTASIS & THROMBOSIS

Question 1

What are the 3 stages of haemostasis? [3]

Answer 1

Primary haemostasis
Platelet adhesion and aggregation

Secondary haemostasis
Formation fibrin network

Fibrinolysis
Clot break down

Question 2

Explain the basic overview from vessel injury –> stable haemostatitc plug

Answer 2

1. Vasoconstriction occurs to reduce blood loss
2. Collagen released is also. This causes platelet released, which in turn causes release of serotonin, TXA ADP & platelet phospholipids.
3. Serotonin then helps with vasoconstriction, whilst **TXAADP helps with platelet aggregation. **
4. Together they help to make a primary plug
5. Through vasoconstriction, shear stress is increased. This cause various molecules to be release, including VWF (important in platelets adhering to vessel walls)
6. Simultaneously to vasoconstriction: tissues factor is exposed. This causes coagulation cascade.
7. Platelet Phospholipid is the surface for many of the coagulation cascade that occurs.
8. Thrombin is created  fibrin
9. together makes stable hameostatic plug

Question 3

Give brief overview on how primary haemostasis occurs to make platelet plug

Answer 3

1. Vessel injury causes collagen to be exposed
2. VWF binds to collagen one side, and the otherside to platelets via glycoprotein 1b receptor
3. Platelets become activated, start clump other platelets. Through glycoprotein IIb, IIIa and fibrin, form stable haemostatic plug.

Question 4

Fill in the differences

Answer 4

Question 5

How can you classify different types of inherited bleeding disorders? [2]

Describe the different types [2]

Answer 5

Distinguish through if primary or secondary haemostasis effected:

Primary haemostasis defects from:
platelet defects:
i) due to number
ii) lack of function
- collagen related disorders: (otherwise can’t initiate primary haemostatic process)

Secondary haemostasis disorders:
Factor deficiency
Antiphosphilipid syndrome

Question 6

Which chromosome is haemophilia caused be a mutation on? [1]

Which coagualtin factors are missing in haemophilia? [2]

Characteristics of disease? [1]

Answer 6

Which chromosome is haemophilia caused be a mutation on? [1]
X

Which coagualtin factors are missing in haemophilia? [2]
Factor VIII or IX

Characteristics of disease? [1]
People with Haemophilia (PWH) do not bleed faster but
bleed for a longer period of time

Question 7

What are the two types of Haemophilia? [2]

How do you tell the difference?

Answer 7

Haemophilia A- Deficiency of factor VIII (1 in every 5000 boy will be born with haemophilia)

Haemophilia B - Deficiency of factor IX (1 in every 30,000 boy will be born with haemophilia)

There are no symptomatic differences between Haemophilia A and B

Question 8

Name classical signs of haemophilia [5]

Answer 8

Big, lumpy bruises

Bleeding into muscles and joints most commonly the knees, elbow, and ankles

Spontaneous bleeding (bleeding inside the body with no clear indication)

Bleeding for a long time after getting a cut, dental extractions or surgery

Excessive bleeding after childbirth in carriers

Serious internal bleeding into vital organs, after an insult (deliberate or accidental)

Question 9

What are the two types of treatment for haemophilia? [2]

What type of medication can you give for haemophilia? [3]

Answer 9

Two types of treatment:
Prophylaxis
On-Demand

Medication:
Factor VIII/ IX- recombinant or plasma (IV)
Desmopresssin / DDAVP (S/C) - causes the release of von Willebrand’s antigen from the platelets and the cells that line the blood vessels where it is stored. Von Willebrand’s antigen is the protein that carries factor VIII.
Tranexamic Acid (IV and Oral) - Antifibrinolytic (stops fribrinlysis)

Question 10

Explain how can target haemophilia with gene therapy

Answer 10

Can temporarily push factor VIII or IX levels up:
- Segment of DNA codes for the specific factor.
- Put gene in adenovirus and put in patient.
- Goes to liver.
- AAV released and makes factor VIII or IX.

Question 11

Role of von Willebrand factor? [2]

Answer 11

Large glycoprotein which forms massive multimers up to 1,000,000 Da in size
1. promotes platelet adhesion to damaged endothelium
2. carrier molecule for factor VIII

Question 12

Von Willebrands Disease:

a) How is it inherited?

b) Which chromosome has a gene mutation to cause it?

c) Basic mechanism?

Answer 12

vWD is an **autosomal hereditary disorder **which is a result of a genetic mutation on chromosome 12

Can be passed from either mother or father and therefore each child has a 50% chance of being affected.

Carries and protects factor VIII when bleeding occurs

Question 13

What are the three different types of VWD?

Answer 13

Type 1– A reduction in von Willebrand antigen and factor FVIII as a result. Autosomal dom
(Quantitative)

Type 2– von Willebrand factor doesn’t work properly and therefore have a low RiCof . Autosomal dom
(Qualitative)

Type 3 – Extremely low levels or complete absence of Von Willebrand antigen, RiCof and factor VIII. Autosomal recessive.
(Quantitative). Most severe

Question 14

Symptoms of VWD? [6]

Answer 14

Frequent nose bleeds
Easy bruising
Gum bleeds (Teeth falling out & extractions)
Menorrhagia
Menstrual bleeding lasting more than 7 days
Intestinal/gut bleeding
Symptoms and their severity vary greatly

Question 15

What are the two types of treatment for VWD? [2]

What type of medication can you give for VWD? [3]

Answer 15

Two types:
Prophylaxis (Type 3 only)
On-Demand

Medication:
(Von Willebrand disease does not require day to day treatment. Management is required either in response to major bleeding or trauma (to stop bleeding) or in preparation for operations (to prevent bleeding):)

Wilate and Voncento- FVIII and vWF (IV)
- DDAVP (S/C) Desmopressin
- Tranexamic Acid (IV and Oral) - stops heavy bleeding