Haematological disease in a child: Haemophilia and von Willebrand Disease (vWB)

Question 1

Define haemophilia A.

Answer 1

Factor VIII deficiency.

Question 2

Define haemophilia B.

Answer 2

Factor IX deficiency.

Question 3

Define von Willebrand Disease.

Answer 3

Inherited deficiency of von Willebrand Factor.

Question 4

Explain the aetiology/risk factors for haemophilia.

Answer 4

Haemophilia is X-linked recessive. Both factors VIII and IX are crucial for thrombin generation via the intrinsic pathway of coagulation. In patients with haemophilia, there is delayed clot formation due to reduced thrombin generation. This leads to the formation of an unstable clot that is easily dislodged, causing excessive bleeding.

Question 5

What are the different levels of severity for haemophilia?

Answer 5

Severe (<1% clotting factor level (CFL)): Frequent spontaneous (occurring with no apparent cause or trauma) bleeding, particularly into joints and muscles; severe bleeding with trauma and surgery.

Moderate (1%-5% CFL): Occasional spontaneous (occurring with no apparent cause or trauma) bleeding; severe bleeding with trauma and surgery.

Mild (>5%-40% CFL): Severe bleeding with trauma and injury.

Question 6

Explain the aetiology/risk factors for von Willebrand Disease.

Answer 6

Abnormalities in expression or function of von Willebrand’s factor (vWF). Usually autosomal dominant and occasionally recessive. There are also acquired forms. vWF is a plasma glycoprotein involved in blood clotting. It acts as an adhesive bridge between platelet receptors (GP-Ib) and damaged subendothelium collagen IV of vessels. It also binds to factor VIII and prevents its degradation.

Question 7

Summarise the epidemiology of haemophilia A.

Answer 7

1 in 5000 boys/men

Question 8

Summarise the epidemiology of haemophilia B.

Answer 8

1 in 30,000 men.

Question 9

Summarise the epidemiology of vWB disease.

Answer 9

Most common inherited coagulation disorder

Question 10

What are the signs and symptoms of haemophilia?

Answer 10

Typical history in a patient with congenital haemophilia includes recurrent or severe bleeding symptoms, or bleeding in unusual sites (e.g., joints or muscles). Minor mucocutaneous bleeding (e.g., epistaxis, bleeding from gums following minor dental procedures, easy bruising) as well as severe bleeding following trauma, surgery, or dental procedures are commonly described.

Question 11

What are the signs and symptoms of vWB disease?

Answer 11

Bleeding disorder which may present with mucocutaneous bleeding (mouth, epistaxis, menorrhagia), increased bleeding after minor trauma or easy bruising.

Question 12

What are some appropriate investigations for haemophilia?

Answer 12

Increased aPTT (measures intrinsic pathway clotting, also used for heparin), normal PT and decreased FVIII/FIX assay.

Question 13

What are some appropriate investigations for vWB disease?

Answer 13

Increased bleeding time, increased APTT, decreased factor VIII, decreased vWF levels. Ristocetin cofactor assay (reduced platelet aggregation by vWF in the presence of ristocetin).

Question 14

What is the general management for haemophilia?

Answer 14

Specialist management and follow-up at a haemophilia centre.

Advice: Avoid antiplatelet drugs (e.g. aspirin), IM injections and contact sports. Hepatitis A and B vaccination. Medicalert card or bracelet. Genetic counselling for patient and family.

Treatment of complications: Specialist referral for complications. A short course of prednisolone may be used to reduce the pain and swelling associated with joint haemorrhage.

Question 15

What is the management for mild haemophilia A (factor VIII 10 % of normal)?

Answer 15

Intranasal or IV DDAVP (vasopressin analogue) increased circulating factor VIII levels via release from endothelial storage sites. Alternatively, oral transexamic acid (a fibrinolytic inhibitor) can be used.

Question 16

What is the management for moderate to severe haemophilia?

Answer 16

Transfusion with factor VIII or IX concentrate (depending on haemophilia subtype) is needed to maintain levels at 20–50 % of normal. Following haemorrhage, the desired factor level depends on the severity and location of the bleeding episode e.g. early joint or muscle bleeding episodes are treated to achieve factor levels of 30–40 %. In severe bleeding, intracranial or intra-abdominal haemorrhage or bleeding in face, neck, and hip, or preoperatively, more rigorous transfusion to 80–100% of normal is necessary.

Question 17

What is the management for vWB disease?

Answer 17

Avoid NSAIDs. DDAVP or tranexamic acid (fibrinolytic inhibitor) for mild bleeding and in minor surgery. Intermediate purity factor VIII concentrate (containing vWF and factor VIII) or specific vWF may be another option.

Question 18

What are the potential complications associated with haemophilia?

Answer 18

Severe and fatal haemorrhage. Crippling joint deformity. 10–15 % of patients develop antibodies to the clotting factor (particularly recipients of factor VIII). Hepatitis C and HIV infection in patients who received clotting concentrates before 1985 in developed countries.

Question 19

What are the potential complications for vWB disease?

Answer 19

Bleeding, antibody formation to exogenous vWF

Question 20

What is the prognosis for haemophilia?

Answer 20

The availability of safer blood products and home treatment programmes mean that most people with haemophilia can lead a relatively normal life.

Question 21

What is the prognosis for vWB disease?

Answer 21

Acute treatment for bleeding or before procedures but normally patients have good response to treatment.