Haemophilia A and haemophilia B
Haemophilia A is a heritable bleeding disorder resulting from
low or, in severe cases, absent functional levels of
coagulation factor VIII. Inheritance is X-linked recessive.
Haemophilia A is the most common of the severe bleeding disorders,
with an approximate incidence of 1 new case per 5,000 male births.
Haemophilia A is caused by mutations in the factor VIII (F8)
Haemophilia B is a heritable bleeding disorder resulting from
low or, in severe cases, absent functional levels of coagulation
factor IX. Inheritance is X-linked recessive. Haemophilia B has an
approximate incidence of 1 new case per 25,000 male births.
Haemophilia A is caused by mutations in the factor IX (F9)
Investigations carried out include familial mutation
identification and interpretation, carrier diagnosis and prenatal
Genetic PND may be performed early in pregnancy, usually via
chorionic villus sampling (CVS) at 11 to 13 weeks of gestation.
This allows first trimester diagnosis, avoiding late termination of
pregnancy. The large majority of patients, following appropriate
expert counselling, do not opt to terminate an affected
Genetic PND may also be performed in the third trimester of
pregnancy, usually at about 36 weeks of gestation, by means of
amniocentesis. This approach enables diagnosis of the presence or
absence of a severe bleeding disorder in the fetus, facilitating
important decisions about the clinical management of
Genetic diagnosis of the causative mutation can provide
important clinical information about the risk for inhibitor
development associated with clotting factor replacement therapy.
This may particularly be valuable in mild or moderate haemophilia
Knowledge of the causative mutation may influence diagnosis and
clinical management in specific cases, for example genetic
diagnosis of haemophilia B Leyden, where the onset of puberty leads
to amelioration of the haemophilia phenotype, or the identification
of mutations associated with a 1-stage/2-stage clotting factor VIII
assay discrepancy in haemophilia A.