Contents
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
- e.g. after circumcision
- Intracranial haemorrhage occurs in about 3% of cases
- Spontaneous bleeding into joints
- Haemarthrosis – can cause chronic deformity, swelling and pain
- Intramuscular haemorrhage
- Can cause compartment syndrome
- 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