Haemophilia

Question 1

What is haemophilia?

Answer 1

A bleeding disorder, usually inherited with an X-linked recessive inheritance pattern, which results from the deficiency of a coagulation factor leading to impaired secondary haemostasis.

Question 2

What causes haemophilia?

Answer 2

1. X-Linked ⇒ primarily affects males, females may be carriers and show mild symptoms (males only have one X chromosome, whereas females have two)
   - ALMOST IMPOSSIBLE FOR FEMALE TO HAVE
2. Haemophilia A (80%) → deficiency of clotting factor 8
3. Haemophilia B (20%) → deficiency of clotting factor 9
4. Vitamin K deficiency

Question 3

What are the risk factors for haemophilia?

Answer 3

Family history, Ashkenazi Jew 

Question 4

Summarise the epidemiology of haemophilia

Answer 4

Due to its inheritance pattern, Haemophilia is mainly seen in MALES
* Haemophilia A incidence: 1/10,000 males
* Haemophilia B incidence: 1/25,000 males
* Haemophilia C is more common in Ashkenazi Jews

Question 5

What are the presenting symptoms of haemophilia?

Answer 5

• Symptoms usually begin in early childhood, or after surgery/trauma
• Swollen painful joints occurring spontaneously or with minimal trauma (haemarthroses)
• Painful bleeding into muscles causing haematomas – high pressure can lead to nerve palsies and compartment syndrome
• Haematuria
• Excessive bruising or bleeding after surgery or trauma
• FEMALE carriers are usually asymptomatic, but may experience excessive bleeding after trauma
• Generally speaking, bleeding in haemophilia is DEEP (into muscles and joints)

Question 6

What signs of haemophilia can be found on physical examination?

Answer 6

• Multiple bruises
• Muscle haematomas
• Haemarthroses (bleeding into joints)
• Joint deformity
• Nerve palsies (due to nerve compression by haematomas)
• Signs of iron deficiency anaemia

Question 7

What investigations are used to diagnose/ montior haemophilia?

Answer 7

1. Prolonged APTT → factor 8 and 9 are in the intrinsic pathway
   - Intrinsic Pathway (APTT) ⇒ 8,9,11,12
   - Extrinsic Pathway (PT) ⇒ 3,7
   - Common Pathway ⇒ 1,2,5,10,13
2. Plasma Factor VIII and IX assay → confirm diagnosis
3. PT (extrinsic pathway) and Bleeding Time → normal
4. Mixing Study → requested if aPTT is prolonged. Correction of aPTT with mixing study suggests coagulation factor deficiency
5. AST and ALT → liver dysfunction may contribute to prolonged PT and aPTT

Question 8

How is haemophilia managed?

Answer 8

1. Substitution of clotting factors → factor concentrates
2. Desmopressin → may be given for mild haemophilia A. Triggers release of VWF from endothelial cells, leading to increase in factor VIII plasma concentration
3. Antifibrinolytic Therapy (eg. Aminocaproic Acid or Tranexamic Acid) → inhibits break down of clots to reduce risk of bleeding
4. Factor IX replacement: minimises the risk of complications

Question 9

What complications may arise following haemophilia?

Answer 9

• Compartment syndrome 
• Allergic reaction to infused product 
• Joint and/or muscular damage 
• Bleeding or life threatening haemorrhage 
• Development of treatment related inhibitors to factor VIII or factor IX 
• Blood-borne infections