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Introduction

Haemophilia B is an inherited X-linked recessive clotting disorder, which can cause excessive bleeding. Haemophilia B causes a similar, but generally less severe disease than haemophilia A.

Most cases are mild, but in severe disease spontaneous bleeding into joints can occur. It is important to treat it effectively to prevent bony deformities and disability caused by these bleeds.

Haemophilia B is one of several genetic inherited clotting disorders, the other most common ones being haemophilia A and von Willebrand’s disease. Haemophilia B is the least common of these disorders.

It is caused by deficiency of factor IX, an important constituent of the clotting cascade.

  • Haemophilia A affects factor VIII
  • von Willebrand’s disease (vWD) also affects factor VIII – although indirectly – von Willebrand factor (vWF) helps to prolong the life of factor VIII, and in vWD, there are defects of vWF
    • von Willebrand’s disease is the most common inherited clotting disorder

Haemophilia B is sometimes called Christmas Disease after the patient in the leading paper on the disease (Mr. Christmas), published in the BMJ Christmas edition 1952.

Epidemiology and Aetiology

  • Affects 1 in 30,000 live births
    • 5x less common than haemophilia A
  • Typically there are “carrier” females and affected males
    • Affected males usually born to carrier mothers
    • 50% chance of a male born to a carrier female being affected
    • Sons born to affected males will not carry the gene nor be affected
    • Daughters born to affected males will be carrier female
  • Spontaneous mutation can also occur
    • Most commonly in Scandinavians
  • Disease severity is related to the circulating levels of factor IX

Pathology

  • Severe disease
    • <1% of circulating levels of factor IX – 50% of cases
  • Moderate disease
    • 1-5% of circulating levels – 30% of cases
  • Mild disease
    • 6-30% of circulating levels – 20% of cases

Occasionally, factor IX antibodies may be the cause – these are known as factor IX inhibitors.

Presentation

  • Top tip:
    • Platelet disorders tend to cause petechial haemorrhage and bruising
    • Clotting disorders tend to cause haematoma and haemarthrosis

Severe disease

  • Typically presents in infancy
  • Spontaneous haemorrhage including haemarthrosis
  • Can start at the time of delivery – especially if instrumental delivery
  • May present with bleeding after circumcision, large haematomas, or joint swellings (haemarthrosis)
  • Mucoasl and GI bleeding can also occurr
    • Melena
    • Frank blood PR
    • Epistaxis
  • Muscular bleeding
    • May cause compartment syndrome
  • Intracranial haemorrhage
    • Irritability
    • Reduced level of consciousness
    • Focal neurological signs

Moderate disease

  • Haemorrhage fro minor trauma, surgical or dental procedures

Mild disease

  • Haemorrhage only typically associated with major trauma or major surgery
  • May be precipitated by NSAID use

Differential Diagnosis

  • Haemophilia A
  • von Willebrand’s disease
  • Vitamin K deficiency
  • Liver disease causing deficiency of clotting factors
  • Platelet disorders

Investigations

  • FBC
    • May be normal or low
    • More likely to be low if recurrent or recent bleeding
  • APTT – prolonged
    • In mild cases may be normal
  • Factor IX deficiency
    • Ask for the “percentage activity factor IX”
  • Factor VIII
    • Normal
    • Should be requested to differentiate from haemophilia A
  • von Willebrand factor
    • Norma;
    • Should be requested to differentiate from von Willebrand’s disease
  • Normal:
    • Platelets
    • PT

Imaging

  • May be useful to assess acute bleeds
  • CT brain for suspected intracranial bleeding
  • X-ray, MRI or USS to assess joints for haemarthrosis

Management

Acute bleeds

  • Recombinant factor IX
  • Aim to correct the factor IX level to 100%
    • Dose is weight based
    • If not available, Fresh-frozen plasma (FFP) is an alternative
  • Typically requires 1-3 doses of recombinant factor IX
    • Usually given 24 hours apart

Long-term management

  • Prophylactic treatment can be given once or twice weekly in severe cases
    • Helps to maintain improved factor IX levels
    • Patients can developed factor IX inhibitors (antibodies) with prolonged treatment
  • Offer vaccination against hepatitis A and B – due to risk of contracting this from FFP
    • Risk is extremely low in modern times as blood products are screened
  • Avoid IM injections (usually can be given SC instead)
  • Avoid NSAIDs
  • Advise patients to wear medical emergency bracelets stating they have haemophilia B, and their usual factor IX levels
  • Avoid contact sports, and sports with a high risk of trauma
  • Avoid manual labour

Prognosis

  • Near normal life expectancy if treated
  • In past decades, use of FFP lead to contraction of hepatitis B and C as well as HIV
    • These patients may have reduced life-expectancy as a result of these diseases
    • Now this is rare due to use of recombinant factor VIII as well as screening for blood-borne viruses in FFP
  • Joint deformities can occur after episodes of haemarthrosis – especially if young when episode occurred

References

  • Haemophilia B - patient.info
  • Murtagh’s General Practice. 6th Ed. (2015) John Murtagh, Jill Rosenblatt
  • Oxford Handbook of General Practice. 3rd Ed. (2010) Simon, C., Everitt, H., van Drop, F.
  • Beers, MH., Porter RS., Jones, TV., Kaplan JL., Berkwits, M. The Merck Manual of Diagnosis and Therapy

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