Haemophilia A
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Introduction

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

It typically presents in neonates and young children, and can occasionally be fatal – usually from an acute intracranial bleed. Most patients have a normal life-expectancy with treatment. In severe cases, it is important to treat it effectively to prevent bony deformities and disability caused by large spontaneous bleeding into joints.

Haemophilia A is caused by deficiency of factor VIII, an important constituent of the clotting cascade.

  • 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 affects factor IX
  • Occasionally haemophilia A can also be caused by an acquired defect – such as antibodies against factor VIII – which tends to occur in older patients

The severity of the disease is related to the levels of functioning factor VIII which remain:

  • Mild disease – >5% factor VIII activity – presents after age of 2
    • About 15-30% of cases
  • Moderate disease – 1-5% factor VIII activity – presents before age 2
    • About 15-30% of cases
  • Severe disease – <1% factor VIII activity – presents in infancy
    • About 40-70% of cases

Epidemiology and Aetiology

  • Range of possible mutations, 30% of cases due to sporadic mutation
  • When inherited – X-linked recessive condition
    • Xq28
    • Typically affects males born to maternal carriers
    • Usually an obvious family history
    • Females born to affected fathers rarely have the disease – only if their mother was also a carrier
  • Prevalence 1 in 5,000
    • 5x more common than haemophilia B
    • Acquired haemophilia affects about 1 per million per year (much rarer than inherited)
  • Marked variability of disease

Presentation

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

Mild disease

  • Typically only causes bleeding after dental procedures, major surgery or trauma
  • Female carriers may also have a slight increased bleeding risk
    • They tend to have factor VIII levels of 10-30% of normal

Moderate disease

  • In addition to events seen in mild disease, also causes bleeding after mild trauma, e.g. venipuncture

Severe disease

  • Bleeding in the neonatal period occurs in up to half of cases
  • Spontaneous bleeding into joints
    • Haemarthrosis – can cause chronic deformity, swelling and pain
  • Intramuscular haemorrhage
  • GI and mucosal bleeding
    • More commonly associated with von Willebrand’s disease and haemophilia B
  • Haematuira
  • Haematoma formation
    • Occasionally may require surgical drainage

Pathology

Low factor VIII levels predispose to bleeding – risk proportional to factor VIII level

  • Mild disease –  (11-30 units/dl) risk after significant trauma/surgery
  • Moderate disease –  (2-10 units) – minor trauma
  • Severe disease –  (<2 units) – frequent, unprovoked bleeds into muscles and joints.  May be 30-50 bleeds a year

Investigations

  • FBC
    • May have low Hb and haematocrit if frequent or recent bleeding
  • Prolonged APTT
    • May be normal in mild disease
  • Normal:
    • PT
    • Bleeding time
    • Fibrinogen
    • von Willebrand Factor (vWF)
  • Diagnosis confirmed by factor VIII assay
    • factor VIII levels low
    • Severity of disease correlates to level of factor VIII

Imaging

  • May be appropriate in situations of acute bleed
    • CT brain if suspected intracranial haemorrhage
    • USS to assess for soft tittle haematoma
    • Joint x-rays may detect effusion from haemarthrosis, but often MRI or USS is required

Differential diagnosis

  • Haemophilia B
  • von Willebrand’s disease
  • Haemophilia C
  • Vitamin K deficiency
  • Platelet disorders
  • Disorders of fibrinogen

Management

Management can be divided into the prevention and treatment of acute bleeding.

Prevention

  • Prophylactic infusions of factor VIII
    • Typically weekly in severe cases
    • The need for prophylaxis is reviewed as the child ages
    • Some patients need life-long prophylaxis
    • Antibodies to factor VIII can develop – making treatment particularly difficult
  • By preventing bleeding in children – particularly haemarthrosis – long term joint deformity and disability can be prevented
  • Avoid NSAIDs
  • Avoid IM injections (usually can be given SC instead)
  • Advise patients to wear medical emergency bracelets stating they have haemophilia A, and their usual factor VIII levels
  • Avoid contact sports, and sports with a high risk of trauma
  • Avoid manual labour

Acute bleeding episodes

  • Administer dose of factor VIII
    • Typically self-administered when bleeding occurs until patient can attend hospital
  • If unsuccessful, then on arrival at hospital:
    • Recombinant factor VIII, OR
    • Fresh frozen plasma (FFP) containing factor VIII
    • Recbominatn factor preferred due to decreased risk of viral transmission
  • Aim to titrate to measurable factor VIII levels in the blood
    • Spontaneous haemarthroses: correct to 30% of normal factor VIII
    • More serious bleeds/surgery: correct to 70-100% of normal
    • Keep these levels for 7-10 days after a severe bleed, and 1-3 days after a minor bleed
  • Desmopressin (DDAVP) may also be used
    • Mobilises stored factor VIII
  • Antifibrinolytics – such as tranexamic acid – may also be used
  • Review the prophylactic regimen after each actor bleed and consider increased doses
  • Patients may develop inhibitors (antibodies which inhibit factor VIII) – managed with porcine factor VIII, activated factor IX, recombinant factor VIIIa and immune tolerance regimens.

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 A - 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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Dr Tom Leach

Dr Tom Leach MBChB DCH EMCert(ACEM) FRACGP currently works as a GP and an Emergency Department CMO in Australia. He is also a Clinical Associate Lecturer at the Australian National University, and is studying for a Masters of Sports Medicine at the University of Queensland. After graduating from his medical degree at the University of Manchester in 2011, Tom completed his Foundation Training at Bolton Royal Hospital, before moving to Australia in 2013. He started almostadoctor whilst a third year medical student in 2009. Read full bio

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