What is the origin of the disease?

Genetic aspects

The gene for factor VIII is located on the long arm of chromosome X. A single allele is present in males compared with two in females. Carriers are generally non-symptomatic although some may have reduced plasma activity of factor VIII (below 50%, i.e. 50 U/dl). They can transmit the anomaly to their offspring

Numerous mutations responsible for haemophilia A have been described and screening involving molecular biology techniques is performed to characterise patients, identify carriers and make prenatal diagnosis. However, these genetic studies are only performed at specialised centres.

In around one third of patients the disease arises following the onset of a de novo mutation in a family hitherto unaffected by the disease.

Physiological aspects

Factor VIII is synthesised by the liver.

It circulates in plasma in a form bound to a transport protein known as Von Willebrand factor (VWF).

The severity of haemorrhagic signs is closely correlated with the degree of deficiency of the coagulation factor in plasma. The severity of the disease is generally identical from one member to another within a given family and does not vary over time.

 

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