Haemophilia

Haemophilia A

Background/Epidemiology

  • Factor VIII deficiency
    • Factor VIII is primarily synthesised by the liver and endothelial cells and has a half life of ~12 hours.  It is protected from proteolysis in the circulation by binding to von Willebrand factor.
  • Affects 1/10000; most common congenital coagulation factor deficiency
    • Varies in severity according to mutation
      • Severe (<0.01U/ml)
      • Moderate (0.01-0.05U/ml)
      • Mild (>0.05 to 0.4U/ml)
  • X-linked disease with 100% penetrance (i.e. all family members have the same gene)
    • As a result, female carries may also have reduced factor VIII levels compared to the general population
  • families with haemophilia A can be offered prenatal diagnosis (chrorionic villous sampling)

Classical_blood_coagulation_pathway

Presentation

  • Severe disease
    • Usually present with spontaneous bleeding into the skin, muscle and joints; retroperitoneal space and intracranially
  • Moderate/mild disease
    • Similar features but associate with trauma rather than spontaneous
  • Bleeding in the large joints and muscles are the major source of morbidity in patients with haemophilia
    • Recurrent haemarthroses causes synovial atrophy, destruction of cartilage and secondary osteoarthritis
    • Therefore, treatment of any hot, red, swollen joint in these patients needs to be prompt
    • Recognising compartment syndrome is also very important and swift management crucial for retaining function

Investigations

  • Imaging of a baby known to have haemophilia should be performed within the first 24 hours of life to look for signs of intracranial bleeding
  • Coagulation screen and measurement of coagulation factors VIII and IX will usually confirm the diagnosis (although exclusion of vWD type 2N should also be considered prior to definitive diagnosis using assays or molecular genetic testing)
  • Imaging should be used in symptomatic patients to look for location and extent of bleeding

Management

  • Severe disease
    • IV infusion of factor VIII concentrate for episode of bleeding
    • Weekly infusions can be given to children but is generally stopped once the patient has reached maturity
      • Patients receiving transfusions should be offered Hepatitis A and B immunisation
      • Patients may develop antibodies against transfused factor VIII (20%)
        • Alternative treatments include transfusions of activated clotting factors e.g. VIIa; or factor VIII inhibitor bypass activity (FEIBA)
  • Mild-moderate disease
    • Vasopressin receptor agonist DDAVP can also help raise vWF and factor VIII by 3-4 fold
      • Monitor for water retention

Haemophilia B

  • Rarer than Haemophilia A (~1:30000)
  • Essentially the same disease but due to a deficiency of factor IX
    • Also X-linked
    • Also similar presentation and variety of severity (practically indistinguishable)
    • Also treated with factor IX replacement transfusion (less risk of antibody resistance)
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