Haemophilia is a genetic and congenital disorder that affects coagulation. Blood does not coagulate properly and, as a result, people with haemophilia have haemorrhage or bleeding episodes of varying severity and in different areas that can arise spontaneously or following trauma.
There are three types of hereditary haemophilia:
- Haemophilia A: inherited as a result of a mutation in clotting factor viii (Factor VIII),
- Haemophilia B: the mutation affects factor ix (Factor IX)
- Haemophilia C: the mutation affects factor xi (Factor XI)
Haemophilia A and B are genetic diseases of the type that are linked to gender or the X chromosome. In 70% of all cases, the mutations are inherited and 30% are ‘de novo’ cases (no history of it in the family). The classic model of inheritance linked to gender consists of women who are carriers of the disease and males who have the illness’ classic and most severe symptoms. That is, haemorrhage episodes or bleeding as a result of a lack of the aforementioned factors. Can women have haemophilia? When both XX chromosomes are affected by the mutation in female embryos, the person will have haemophilia. In the large majority of these cases, the pregnancy does not progress and ends in pregnancy loss. Whilst there have been documented cases of women with haemophilia, it is incredibly rare.
Inheritance of haemophilia A and B is represented in the figure:
The inheritance pattern in haemophilia C is different. More specifically, it is an autosomal recessive inheritance and it can, therefore, be present in both men and women. Inheritance of haemophilia C is represented in the figure below:
Whilst haemophilia is not a very common disease, the seriousness of the haemorrhage episodes and their repercussions or medical consequences in the long term can be significant.
Identifying all female carriers is a key objective.
Diagnosis is based on family background (family tree) and determination in blood of the coagulation factors in each case (8, 9 and 11) although the final test consists of identification of mutations in the related genes by means of molecular genetics tests in carriers or sufferers.
When a woman is diagnosed as being a haemophilia carrier, and with reference to reproduction, she should be informed of all the options for diagnosis so that genetic guidance can be given prior to pregnancy (preconception counselling).
In reproductive medicine, pre-implantation genetic diagnosis (PGD) is the technique that means that embryos affected by a hereditary disease can be identified. It consists of analysing a sample of cells from embryos obtained during in vitro fertilisation treatment. The purpose is to detect specific mutations for each illness that is analysed and to transfer only embryos obtained that are free of serious genetic abnormalities.
PGD can also be used in gender-related hereditary illnesses in order to identify only the gender of the foetus and transfer only XX embryos (girls).
If a female carrier is already pregnant, there are several options for prenatal diagnosis:
- Invasive prenatal diagnosis: obtaining DNA from the foetus in order to study the mutations by means of a chorionic villus biopsy (chorion biopsy) between weeks 10 and 12 of pregnancy, amniocentesis (weeks 15 to 17) or cordocentesis (taking a blood sample from the umbilical cord between weeks 16 and 21).
- Non-invasive prenatal diagnosis: the gender of the foetus but not the mutation can be determined by assessing cell-free foetal DNA in maternal serum or plasma. If the result is male, it is not possible to determine if the foetus is healthy or affected by the illness. If the result is female, she may or may not be a carrier (with no symptoms).