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 characterize patients, identify carriers and make prenatal diagnosis. However, these genetic studies are only performed at specialized centers.
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.
Factor VIII is synthesized 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.