Prevention of Hemophilia: Carrier Detection and Prenatal Diagnosis

With the advent of modern technology in medical sciences, it is now possible to have a choice open to the couples planning their families. When there is a family history of hemophilia it is now possible to identify almost accurately most females who carry the hemophilia gene. Women, who know they are carriers, or might be carriers, may have options for prenatal diagnosis to obtain information on fetal status.

Who is a Carrier? Hemophilia is a classic example of a sex linked recessive disorder. The genes that control the production of factor VIII and factor IX are located on the X chromosome. Males have one X and one Y chromosome whereas females have two X-chromosomes and no Y. Therefore, the defect in the factor VIII or IX genes on the X chromosome causes their relative deficiency and leads to a person with hemophilia (PwH) in case of a male or carrier in case of a female.

A PWH passes his abnormal X gene to all of his daughters and his normal Y to all his sons. Therefore, all his sons are essentially normal individuals whereas all his daughters become carriers of hemophilia. Similarly, carrier females having the defective X chromosome can give birth to a carrier daughter or son with hemophilia with a 50:50 chance in each pregnancy. Hence, the carriers of hemophilia are the descendants of a hemophilic father or a carrier mother. The status of a carrier can well be identified as obligatory carrier and possible carrier by their family history or family tree.

A woman is an obligatory carrier if:

 * Her father has hemophilia.
* She has one son with hemophilia and affected close relatives like brother and maternal uncle.
*She has one son wiith hemophilia and her sister(s) has a hemophilic son.
* She has two or more sons with hemophilia.

A woman is a possible carrier if:

* She has one or more maternal relatives with hemophilia or her sister(s) has affected son.
* She has one son with hemophilia and no other affected relatives.

Most carrier women do not show any symptoms of bleeding characteristic of hemophilia. But few with low levels of factor VIII or factor IX activity may face some bleeding problem at the time of surgery or have some other symptoms like excessive or extensive menstrual bleeding period, blue patches on the body etc.

Since hemophilia is presently not a curable disorder and can pass through families, it can only be prevented. The prevention is possible by diagnosing the status of a female carrier by carrier detection and next by selection of birth by performing pre-natal diagnosis. These tests are done in special laboratories by adopting DNA analysis method. These methods are up-to >90% accurate in their analys1s.

For Carrier Detection 10 ml of blood sample should be collected in an EDTA Vacutainer from the person affected with hemophilia, his father, mother and also the sister(s) whose carrier status to be detected. The vials should be clearly labeled with name and relation and transported to the detection center preferably within 24 hours, after making prior arrangements.

It should be noted that this process of DNA analyzing also needs to identify the informative marker in the families, which takes time, and it may even be difficult to identify in about 20% of families.

For Pre-natal Diagnosis Between 10 to 12 weeks of pregnancy, fetal DNA can be obtained from the Chorionic Villi (CVS) from amniotic fluid (AF) between 14 to 18 weeks and from fetal blood sample (FBS) between 16 to 20 weeks. These procedures can be performed in specialized hospitals and the sample be analyzed in special laboratory for establishing the status of the baby in the womb.

The prevention of hemophilia by carrier detection and prenatal diagnosis and subsequent selective abortion should always be done after proper and effective counselling to the family members of the PwH. Children should preferably be informed about their carrier status when they are able to fully understand it (after they attain the age of majority i.e. 18 years). Generally the family members suffer from tremendous mental stress after knowing the carrier status. Therefore it is very important that they are counseled by a skilled genetic counselor with enough knowledge about Hemophilia and who can facilitate decision making, taking special care about the feeling of guilt about their choice. It is also important not to neglect the PwHs themselves in discussing the genetic aspects, to be sure that they are aware of the fact that all of their daughters will be carriers. The earlier the counselling is provided, the lesser the emotional impact concerning maternity and abortion is expected to be.

However, if you want to go in for Carrier Detection or Pre-natal Diagnosis, information on where to go for help has been included in this booklet.

Further Please Note:

  1. If you are pregnant and want to know the status of your baby in the womb, do not cross the limit of the weeks described above for the respective diagnosis tests.
  2. Send the blood samples as described through courier service (preferably by DHL/Blue Dart etc.) so that it ensures a safe reach to the destination within 24 hrs.
  3. It is preferable that you are mentally prepared to take a decision for an abortion (in case of an affected baby) after a genetic counselling.

Names & Addresses of the Centers for Diagnosis

All India Institute Of Medical Sciences
Deptt.Of Genetic Medicine
New Delhi-110029
Sir Ganga Ram Hospital
Deptt. of Genetic Medicine
Rajendra Nagar
New Delhi
King Edward Memorial Hospital & Institute of lmmuno Haematology I.C.M.R,
13th Floor, Hospital Campus, Parel,
Mumbai-400 012
Christian Medical College & Hospital
Deptt.Of Genetic Medicine
Vellore-632 004
Indian Institute Of Chemical Biology
Deptt. Of Human Genetics
4, Raja.S.C.Mallick  Road, Jadavpur,
Kolkata-700 032
Centre For Cellular And Molecular Biology
Uppal Road, Hyderabad-500 007