What is Haemophilia A

Haemophilia A involves a genetic defect causing abnormality of blood clotting. Normal blood contains a range of special proteins and chemicals that cause blood to clot quickly if blood vessels are damaged. This occurs due to a sequence of events known as the ‘coagulation cascade’, involving a series of reactions between different coagulation ‘factors’. The end result is a mesh of protein called ‘fibrin’, which is the solid part of a clot, and plugs up the damaged vessel.

In Haemophilia A, levels of a coagulation factor called Factor VIII are reduced. This occurs due to genetic defects in the gene coding for this protein.

Statistics on Haemophilia A

The prevalence of heamophilia A is about 1 in 5000 in the male population. It is only present in males because the gene for Factor VIII is on the X chromosome; males only inherit one X chromosome, and so if this has the defect, then they will suffer haemophilia. Females inherit two X chromosomes, and so even if one has the defect, they will not suffer from haemophilia, as the other chromosome has a normal Factor VIII gene.

Females with one abnormal X chromosome are called ‘carriers’. If a female carrier has a son, he has a 50% chance of having haemophilia, and a daughter has a 50% chance of being a carrier. All daughters of haemophiliacs are carriers and the sons are normal.

Risk Factors for Haemophilia A

As explained above, a family history is clearly a predisposing factor for haemophilia. In addiotion, about one-third of cases are ‘sporadic’, meaning that the genetic defect occurs for unknown reasons, without being passed on from the patient’s parents.

Progression of Haemophilia A

As the disease arises from an abnormality in a gene coding for a protein that is important to coagulation throughout life, haemophilia is an immediate, constant and unremitting disease. However, cases vary in severity, depending on the level of Factor VIII in the body.

In milder cases, diagnosis may not be made until quite late in life. In addition, effective treatment is available, meaning that patients may show considerable improvement once this has begun.

How is Haemophilia A Diagnosed?

 

  • Full blood examination– this will usually be normal, apart from lowered haemoglobin if the patient has become anaemic due to blood loss.
  • Coagulation studies – the following important tests of blood coagulation and coagulation factors will be altered: PTTK (APPT) – increased; VIII:C – markedly decreased.

    Prognosis of Haemophilia A

    The most frequent cause of death in patients with severe haemophilia was cerebral haemorrhage; it is now AIDS. Although HIV transmission by blood transfusion is now very rare in the developed world, HIV was transmitted to many haemophiliacs by coagluation facor concentrates between 1979 and 1985.

    How is Haemophilia A Treated?

    Not surprisingly, the treatment for haemophilia A is replacement of Factor VIII. This is achieved by the administration of Factor VIII from donated blood, or by artificially synthetised Factor VIII.

    The advantage of the ‘artificial’ (recombinant) Factor VIII is that it doesn’t involve the (very small) risk of transmission of infectious diseases that is inherent to transfusion of blood products. However, the recombinant Factor VIII is very expensive.

    Factor VIII may be given immediately after bleeding has started, or in severely affected patients, three times weekly to prevent bleeding from occurring.

    Note that some haemophiliacs develop an immune response against Factor VIII. In these cases, even administering very high doses of Factor VIII does not significantly improve blood coagulation. Treatment is difficult; several approaches have been attempted with some success: factor IX concentrates, recombinant factor VIIa, immune tolerance induction.

    Haemophilia A References

    [1] Kumar P, Clark M. Clinical Medicine. Fourth Ed. WB Saunders, 1998. pp 404 -406
    [2] Talley NJ, O’Connor S. Clinical examination. Third Ed. MacClennan & Petty, 1996. p227