Three years ago Lisa Webb,* of Rochester, New York, was shocked to learn that her newborn son, Matthew, had severe hemophilia A. His condition was diagnosed when an IV inserted to administer antibiotics soon after birth caused his hand to swell “like a purple glove,” Webb says. Nurses also noticed blood oozing from the various routine needle sticks Matthew underwent. “Within 48 hours of delivery, they had done a clotting test,” Lisa recalls. “He was then transferred to a larger neonatal intensive care unit for further diagnosis and CT scans to make sure there was no internal bleeding.” Matthew has been on prophylaxis since he was 18 months old and has experienced no major problems.
Unaware of any history of bleeding disorders in her family, Lisa was anxious to find out if her son’s hemophilia was inherited or the result of a spontaneous genetic mutation. She underwent tests that revealed that she is not only a carrier, but also among the approximately 1/3 of carriers whose factor levels are below normal. Lisa’s level is 25%; the normal range is 50% to 150%.
Such factor level information, easily obtained through blood screening, can help women manage their own health, make informed reproductive decisions and alert female relatives who also may be affected and want to be tested, says Kim Provenzano, a nurse practitioner who specializes in genetic counseling at the Mary M. Gooley Hemophilia Center in Rochester, New York.
Testing Factor Levels
A simple factor level test could reveal if a woman is a carrier. If her factor levels are low, she carries the gene for hemophilia. It also can indicate that she may be at some risk of bleeding. “In some women who are carriers, the normal X chromosome they received from their mother undergoes inactivation, and because of that they produce less than 50 percent of factor VIII or IX,” explains Dr. Peter Kouides, medical and research director at the Mary M. Gooley Hemophilia Center. “This places them at risk of bleeding during surgical or dental procedures and childbirth.”
Low factor levels may also have a beneficial effect for some women. Researchers in the Netherlands reported in the medical journal Lancet in 2003 that carriers are less likely to die from heart disease because decreased blood clotting reduces the risk of blocked arteries—similar to the effect obtained from taking an aspirin a day.
A more complex blood test analyzes the X chromosome to identify the exact mutation that causes hemophilia in a family. In Lisa’s case, “she and her son have the classic hemophilia gene mutation that we see in about 40% of our patients,” says Kouides. “This involves an inversion of a segment of the DNA that is termed intron 22.”
But the test is expensive, costing anywhere from $400 to $1,000, and not all insurance companies cover it. It also is not foolproof. In fact, it may not yield the desired information even with the most detailed genetic analysis. “It’s sometimes difficult for people to understand that you may not find a genetic mutation but you may still carry hemophilia,” says Provenzano. “It may be a mutation that’s not known or that current technology cannot find.”
If there’s a family history of bleeding disorders, and a woman already knows she is a carrier, the genetic test is unnecessary, says Kouides. However, in about a third of cases, a genetic defect is present in the son but not the mother, which means that hemophilia was the result of a spontaneous mutation in utero. The woman’s future children would have no increased risk of the disorder.
A woman who has the mutation has the same chance with each pregnancy—25%—of giving birth to a boy without hemophilia, a girl who is not a carrier, a boy with hemophilia or a girl who is a carrier. That knowledge could affect a woman’s decision to have more children.
A woman with the genetic mutation also can be tested during pregnancy to determine if the fetus is a boy with hemophilia. Such information can prepare the parents emotionally, as well as perhaps spark a discussion with the doctor about whether a caesarean delivery may be necessary to prevent possible bleeding in the brain as the baby passes through the birth canal.
Ideally, testing for factor levels and for the hemophilia gene should extend to the daughters of carriers, who have a 50% chance of being carriers themselves. Lisa plans to have her daughter, now 15 months old, tested when she approaches adolescence, or earlier if she needs surgery or major dental work.
Lisa encourages women who may be carriers to get tested. “It’s definitely not a negative thing,” she says. “I don’t look at being a symptomatic carrier as the end of the world. It’s just one more thing I have to consider.” Knowing your factor level “can answer some questions for women who may have unusually heavy periods or whatever,” she notes. As for genetic testing, “it can be helpful to know you’re going to have a child with special needs that you’re going to have to deal with. Some people may not view a child with hemophilia the way I do, and maybe that’s something they wouldn’t want for their lives, so in that case it could be helpful to know [they are carriers] prior to the childbearing years.”
“It’s never an easy diagnosis,” Lisa says. “I would never wish for any different than what I have. I’m blessed to be part of the hemophilia community.”
* Names have been changed