Go down the internet-search rabbit hole in pursuit of information about hemophilia, and you will immediately discover that this fairly common bleeding disorder is — as the CDC's information page about hemophilia says, for instance — " is usually an inherited bleeding disorder". "Usually" doesn't mean "always", and an important Italian study published in the journal Haemophilia in January 2022 in fact reveals that a large majority of babies born with a severe form of hemophilia had no family history of the bleeding disorder.
What's going on here? What should you know about a person's risk of being born with hemophilia, perhaps especially if you are currently trying to conceive?
What Is Hemophilia?
Hemophilia is a serious bleeding disorder that impacts their blood's ability to clot — leading to a profound risk of prolonged bleeding that is hard to stop, both following injury or surgery, or seemingly spontaneously. In healthy people who encounter an injury that causes bleeding, platelets and clotting factors instantly rush to the site. The body then starts working on forming a clot that will stop the bleeding, a process that can be very fast in the case of small cuts.
Patients with hemophilia lack the necessary clotting factors to make this possible, and can have very low levels of either factor VIII (hemophilia A, also called classic hemophilia) or factor IX (hemophilia B, also called Christmas disease), or completely lack these clotting factors. The results include bleeding into the joints that causes stiffness and pain, nosebleeds that occur spontaneously and are very challenging to stop, easy bruising (bleeding under the skin), hematoma (blood accumulation under the skin), bleeding gums, and a high risk of hemorrhage after surgery or more extensive injuries.
To save their lives, people with hemophilia will sometimes need blood transfusions, a fact that has historically placed patients at risk of blood-borne diseases such as viral hepatitis and HIV — a risk that remains very real in some regions of the world. In rare cases, hemophilia can be fatal.
Understanding the Cause of Hemophilia
Some cases of hemophilia are acquired later in life. Most people who have hemophilia are, however, born with it. In that case, hemophilia is called by a specific gene mutation. Because this gene mutation is inherited, most people who have hemophilia will already have relatives who also have the bleeding disorder.
Hemophilia, which is far more common in males than in females, is inherited in this pattern:
- The gene mutation that causes hemophilia is located on the X chromosome, which men inherit from their mothers. Females, who have two X chromosomes, get one from each parent.
- If the mother is a carrier of the gene that causes hemophilia but the father is not affected, their son has a 50 percent risk of being born with the disorder, while their daughter has a much lower risk — but still has a 50 percent risk of carrying the gene, which can later be passed on to a son.
- If the father carries the gene for hemophilia but the mother does not, all sons will be unaffected — but daughters will have a 50 percent risk of carrying the gene, which can later be passed on.
- Female carriers, who are called heterozygous, can pass the genes on through many generations without symptoms ever being apparent.
What Did the New Study Find?
The study, entitled The effect of carriers’ reproductive choices and pregnancy history on sporadic severe haemophilia: A 20-year retrospective study through a regional registry, examined births over the last two decades through the Emilia-Romagna Regional Haemophilia Registry in Italy. The study was launched after it became apparent that a shocking number of babies were being born with severe hemophilia in this Italian region, but that these cases were sporadic — appearing without a known family history.
“More than two thirds of persons with severe hemophilia are sporadic cases,” the research team said. Why?
Their research subjects offered clues.
- 94 of the 104 mothers, who had children with hemophilia, were shown to be carriers.
- 37 were found to have relatives who had a known family history of hemophilia.
- 57 were related to people who had "sporadic" hemophilia cases, not connected to a known family history.
The study revealed that a significant minority — 47 percent — of mothers who knew they carried the hemophilia gene opted to undergo prenatal diagnosis, while those with previously identified sporadic cases in their families often chose not to get pregnant again. This means that, far from there being a sudden "outbreak" of hemophilia cases, as iy were, the increase in sporadic cases is likely due to the fact that people who know they have a family history of hemophilia are opting to go through genetic counseling to reduce the risk of having children with the bleeding disorder.
Studies like these reveal that hemophilia genes can stay hidden for a long time in female lines where no symptoms are present, and may provide interesting insights in future.