Hemophilia Carrier Testing
Only women can carry the gene that causes hemophilia. So whenever a child is diagnosed with hemophilia, the carrier status of women in that family becomes a concern. In 5% of the cases, women who are carriers of the gene have symptoms of hemophilia, most occurring during tooth extractions, surgery, and childbirth.
This section on Hemophilia Carrier Testing covers:
- How Do You Become a Hemophilia Carrier?
- Who Should Be Tested for Carrier Status?
- When Should Carrier Testing Be Done?
- What Kind of Tests Are Used?
How Do You Become a Hemophilia Carrier?
Hemophilia is caused by a problem in one of the genes that tells the body to make the clotting proteins (called coagulation factor). These genes are located on the X chromosome.
- All males have one X and one Y chromosome (XY)
- All females have two X chromosomes (XX)
A female who inherits one affected X chromosome is said to become a carrier of hemophilia. In other words, she carries the gene that causes hemophilia on a chromosome. She can pass the affected gene to her children. Daughters of males with hemophilia always carry the hemophilia gene.
A woman is always a carrier if she is:
- The biological daughter of a man with hemophilia
- The biological mother of more than one son with hemophilia
- The biological mother of one son with hemophilia and has at least one other blood relative with hemophilia
A woman may or may not be a carrier if she is:
- The biological mother of one son with hemophilia
- The sister of a male with hemophilia
- An aunt, cousin, or niece of an affected male related through the mother
- The biological grandmother of one grandson with hemophilia
Sometimes a baby will be born with hemophilia, but doesn’t have a family history of the bleeding disorder. If the baby is the first one in the family with hemophilia, the mother might be a carrier. It’s possible that the hemophilia-causing gene did not exist in the mother, thus it was never passed down to the child. In this case, the mother isn’t a carrier and the hemophilia is caused by a new change in a gene, called a spontaneous mutation.
What are the chances?
If the baby’s biological father does not have hemophilia, a pregnant woman who is a carrier of hemophilia can expect 1 in 4 possible outcomes:
- A girl who is not a carrier (25% chance)
- A girl who is a carrier (25% chance)
- A boy without hemophilia (25% chance)
- A boy with hemophilia (25% chance)
To make it simple: a woman who is a carrier has a 25% (one in four) chance of having a son with hemophilia with each pregnancy. In rare cases, a girl may also be born with hemophilia when the father has hemophilia and the mother is a carrier.
Who Should Be Tested for Carrier Status?
The National Hemophilia Foundation’s Medical and Scientific Advisory Council (MASAC) recommends that girls and women who are at risk of being a hemophilia carrier be tested before they become pregnant. Testing clotting factor levels is a first step to help learn if a woman carries the hemophilia gene. If the clotting factor test results are uncertain, MASAC recommends genetic testing to determine if a woman is a carrier.
Hemophilia carrier testing can provide valuable information for women and their families. Testing for factor levels and carrier status can help women manage their own health, make wise reproductive decisions, and alert female relatives who also may be affected and want to be tested.
For more information, go to MASAC Guidelines #192.
Symptomatic carriers should take the same precautions as patients with mild hemophilia. They should:
- Be cautious about participating in contact sports
- Avoid taking over-the-counter (OTC) medicines, such as aspirin, ibuprofen, and other non-steroidal anti-inflammatory drugs
- Carry appropriate medical identification
A woman who is or might be a hemophilia carrier should ask her female relatives about any bleeding problems they might have.
When Should Carrier Testing Be Done?
There is no right age to test a woman’s hemophilia carrier status. Some families delay testing; others test a child who may be a carrier early so any necessary precautions can be taken. Typically, females are tested for carrier status when they are old enough to make an informed decision, usually some time after menarche. Even if the carrier status is unknown, medical professionals recommend that possible carriers get their clotting factor levels tested early in life and before a planned surgical procedure. Some women may want to wait until pregnancy to determine their carrier status. However, testing before pregnancy is more prudent. One reason is that clotting factor levels rise during pregnancy, making tests results unreliable. Moreover, the results of genetic testing may not be available for weeks.
Delivering the proper care
Pregnant carriers should notify their obstetrician/gynecologist and plan for the delivery and possible care of a baby with hemophilia. Hospital staff must be prepared to provide appropriate treatment for the mother and child. Labor and delivery pose potential threats to babies with hemophilia because of the trauma related to the birthing process. A baby with hemophilia should not be delivered with forceps or suction extraction (called vacuum delivery); some doctors and women may opt for cesarean delivery, which can help reduce the risk of injury to the baby.
What Kinds of Tests Are Used?
With so many options, hemophilia carrier families considering their first or subsequent child benefit enormously from genetic counseling, which is available through most Hemophilia Treatment Centers (HTCs). Highly trained genetic counselors provide extensive information and support for carriers and their families prior to actual carrier testing, before they conceive a child, and after the unpredicted birth of a son with hemophilia. Carrier testing is a very personal decision.
Types of Tests
- Family tree. The first step in finding out whether a woman is a hemophilia carrier is getting a detailed family history. As part of genetic counseling, a physician or genetic counselor will take a family history and draw a family tree, called a pedigree chart. In general, the pedigree chart contains information on 3 generations: children and cousins; parents, aunts, and uncles; and grandparents. The pedigree helps identify people within the family who could be carriers of the gene
- Factor Levels. Blood tests are performed to measure levels of clotting factors VIII (8) and IX (9). Factor level tests are 70% to 90% accurate in determining a person’s carrier status. On average, carriers have lower levels of factor VIII (8) or IX (9) in their blood than women who are not carriers. Although carriers have only one normal X chromosome, their clotting factor levels aren’t half of the normal level. Indeed, normal covers a wide range of clotting factor levels. Carriers and noncarriers often have similar clotting factor levels. In addition, age, health status, pregnancy, nursing, and medications, including birth control pills, can affect clotting factor levels. Knowing that a woman’s clotting factor level is low can help doctors provide the best care in situations involving bleeding, such as surgery or dental procedures. Female carriers with clotting factors that are less than 50% of normal can also have menorrhagia and joint bleeds
- DNA Testing. The most accurate way to tell whether a woman is a carrier is to examine her DNA for genetic changes that cause hemophilia. Questions concerning a certain method or laboratory test should be referred to a genetic counselor, but a few basics are below
There are 2 types of DNA analysis available:
Direct Mutation TestingFor hemophilia A and B, it is possible to look for mutations within the factor VIII (8) and factor IX (9) genes, respectively. This approach is called direct mutation testing and is the most accurate method for identifying carriers. A blood sample from the male family member with hemophilia is checked first. In about 98% of cases, a mutation can be identified
Next, a blood sample from the woman desiring carrier testing is obtained and her DNA is checked for the specific mutation. If the mutation is found in the female’s DNA, she is a carrier; if the mutation is not found, then in most cases she is not. (In rare instances, a woman’s eggs but not her blood cells have the mutation)
Even in families with no living males, direct detection methods may provide helpful information. Sometimes a mutation that is known to occur in other individuals with hemophilia is found, suggesting that a woman may be a carrier. This testing is performed at specialized laboratories. Typically, results are available in a few weeks
Linkage (Indirect Testing)In some cases of hemophilia A and hemophilia B, a gene mutation cannot be identified. Using indirect testing (called linkage testing) may help determine the gene carrier status of females by tracking the gene in the family. To perform this test, blood samples are taken from the male with hemophilia and other family members. Patterns of linked DNA in the person with hemophilia are compared to the DNA in family members to check for the same pattern. Linkage testing is not as accurate as direct testing and does not provide information for all families. A genetic counselor can discuss the benefits and limitations of this type of testing for a specific family
- Prenatal Testing
In families with a history of hemophilia, prenatal testing is an option to see if the fetus is affected. This testing can be done early in the pregnancy, allowing the family to make informed decisions and preparations. Such information can help prepare the parents emotionally, as well as to talk with the doctors about plans for delivery. Some tests require a small sample of the amniotic fluid, placenta, or blood from the umbilical cord. If you are pregnant and you think you could be a carrier, or if you have one child diagnosed with hemophilia and you are expecting again, talk with your obstetrician about what precautions should be taken to ensure a safe delivery for you and your child
- Tests for von Willebrand Disease (VWD)
Several tests can be used to look for mutations in the von Willebrand factor (vWF) gene. These mutations are, however, much more likely to be present in the more severe forms of VWD than the milder ones
A family practitioner, internist, obstetrician/gynecologist, or pediatrician can refer a person interested in learning if they have a vWF gene mutation to a hematologist or Hemophilia Treatment Center (HTC) for testing. Because not all laboratories are able to perform these tests, traveling to get tested is likely
For more information, go to MASAC Guidelines #192.
Coping With Being a Hemophilia Carrier
Learning that you or someone you care for is a hemophilia carrier can be an emotional and challenging time. How you feel about knowing that you or the person in your care is a carrier often depends on experience with members of the family who have been dealing with hemophilia. A father and brother’s attitude to having or not having hemophilia can also affect your reaction. Use available support from HTC genetic counselors and local or online support groups.
How a person deals with the possibility of passing hemophilia on to a child depends on many, often complicated, factors. Genetic counselors can help as decisions are made about parenthood, whether to continue with a pregnancy, childbirth, and raising a child with a chronic health condition. Issues affecting the decision-making process may include the severity of the hemophilia that occurs in the woman’s family and her own desires, culture, and religious beliefs, as well as those of her partner.
Couples can and should turn to trusted family members, friends, and professional advisors to talk about the personal and emotional aspects of testing and test results. The physician, nurse, and social worker at an HTC can provide information on the health issues, financial matters, and practical aspects of raising a child with hemophilia. Genetic counselors can also help families better understand their emotions, as well as address their concerns.