Haemophilia

Question 1

Definition of haemophilia

Answer 1

Is a bleeding disorder that is usually inherited with an X-linked recessive inheritance pattern. Would result from the deficiency of a coagulation factor

Question 2

Aetiology of haemophilia

Answer 2

• Haemophilia is usually inherited from an X-linked recessive inheritance pattern.
◦ This hence means males are exclusively affected, females can be carriers
◦ However, there is a relatively high rate of new mutations, so some patients may not have a family history

• There are 3 subtypes of haemophilia:
‣ Haemophilia A:
◦ Results from the deficiency of clotting factor VIII

				‣ Haemophilia B:
						◦ Results from the deficiency of clotting factor IX

				‣ Acquired Haemophilia: non-inherited condition that is completely separate and arises from autoimmune causes

Question 3

Pathophysiology of haemophilia

Answer 3

• Deficiency of either factor VIII or IX would affect thrombin generation via the intrinsic pathway of coagulation. This would result in failure to generate fibrin to stabilise the platelet plug. This can cause excessive bleeding

Question 4

History and Examination of haemophilia

Answer 4

• History of recurrent or severe bleeding:
◦ Can be spontaneous or trauma induced bleeding into joints and muscles.
◦ There may be excessive bleeding after surgery, after dental procedures. The onset may be delayed by several days
• Haemarthrosis: Is a hallmark of haemophilia= spontaneous joint bleeding. Presents with swelling of the joints (commonly elbow, knees etc), pain and decreased range of motion
• Bleeding into muscles: Very common symptom of haemophilia
• Prolonged bleeding common
• Excessive bruising /haematoma: IM injections would lead to extensive haematoma, so avoid them

Question 5

Risk factors for haemophilia

Answer 5

• Family history of haemophilia
• Male sex

Question 6

Investigations for haemophilia

Answer 6

• Activated partial thromboplastin time (aPTT): Usually prolonged. May not be prolonged in mild cases
• Plasma factor VIII and IX assay: Should be ordered to confirm diagnosis along with aPTT and to assess severity

• FBC: to rule out thrombocytopenia as a cause of bleeding
• Prothrombin time: used to assess the extrinsic and common pathway

Question 7

Treatment for haemophilia

Answer 7

Life threatening/limb threatening bleed:
1) Factor concentrate: Bleeds include those intracranial, GI or airway. Factor VIII or Factor IX should be administered URGENTLY
+ Supportive care and specialist advice: ABCDE

Non-life-threatening: Mild haemophilia A:
1) Desmopressin + Supportive care: Can be given intranasally as an outpatient. Can increase the factor VIII levels

Non-life-threatening: Moderate-severe Haemophilia A or Haemophilia B:
1) On demand factor concentrate + supportive care: Give the appropriate factor concentrates every 12-24 hours until symptoms resolve

Prophylaxis for Haemophilia A:
Emicizumab is a prophylactic agent that can be given to reduce the risk of joint damage/bleed

AVOID NSAIDs and IM INJECTIONS

Question 8

Prevention and prognosis of haemophilia

Answer 8

Secondary prevention can be considered in the form of Emicizumab as prophylaxis for severe Haemophilia A

Treatment allows for near-normal lifestyle and lifespan of patients. Preservation of joint function may be achieved with the use of prophylaxis, administering haemostatic agents etc

Question 9

Complications of haemophilia

Answer 9

• Compartment syndrome
• Joint or muscular damage: high risk of severe haemophilia and not receiving prophylaxis. Chronic joint arthropathy
• Bleeding or life-threatening haemorrhage