Hemophilia is caused by mutations in genes that tell your body how to make blood-clotting proteins. Without enough of these proteins, blood cannot clot properly after an injury, surgery, or sometimes for no obvious reason at all. The specific gene affected determines which type of hemophilia a person has, but nearly all forms trace back to a problem on the X chromosome.
The Genetic Root: Missing Clotting Proteins
Your blood relies on a cascade of proteins to form clots. Hemophilia occurs when one of these proteins is either missing, produced in reduced quantities, or made in a form that doesn’t work correctly. Two genes are responsible for the vast majority of cases:
- Hemophilia A results from mutations in the F8 gene, which provides instructions for making clotting factor VIII. It’s the more common form, occurring in roughly 1 in every 5,617 male births in the United States.
- Hemophilia B results from mutations in the F9 gene, which codes for clotting factor IX. It’s less common, affecting about 1 in 19,283 male births.
The type of mutation matters for severity. Mutations that completely wipe out the activity of a clotting factor cause severe hemophilia, with spontaneous bleeding into joints and muscles. Mutations that reduce but don’t eliminate the protein’s activity tend to cause mild or moderate forms, where abnormal bleeding may only show up after surgery or a significant injury.
Why It Runs in Families: X-Linked Inheritance
Both hemophilia A and B follow an X-linked recessive inheritance pattern. The F8 and F9 genes sit on the X chromosome, one of the two sex chromosomes. Males have one X and one Y chromosome, so a single mutated copy of either gene is enough to cause the condition. There’s no backup copy to compensate.
Females have two X chromosomes, which usually provides a safety net. If one copy of the gene is mutated, the other can typically produce enough clotting factor to prevent symptoms. This is why hemophilia overwhelmingly affects males, while females with one altered gene are often called carriers.
A key detail of X-linked inheritance: fathers cannot pass the condition to their sons. A father passes his Y chromosome to sons and his X chromosome to daughters. So a man with hemophilia will have daughters who are all carriers, but none of his sons will be affected (assuming the mother doesn’t also carry the gene). A carrier mother, on the other hand, has a 50 percent chance of passing the mutated X chromosome to each child. That means each son has a 50 percent chance of having hemophilia, and each daughter has a 50 percent chance of being a carrier.
When There’s No Family History
About 30 percent of hemophilia cases arise in families with no prior history of the condition. These are caused by spontaneous (de novo) mutations that occur randomly during the formation of eggs or sperm, or early in embryonic development. A child can be born with hemophilia even though neither parent has a known mutation, which is why the diagnosis sometimes comes as a complete surprise after an unexplained bleeding episode.
Females Can Have Symptoms Too
The idea that hemophilia only affects males is a simplification. Women who carry one mutated copy of the gene can have low clotting factor levels and real bleeding symptoms. This happens partly through a process called X-inactivation: in every cell, one of a woman’s two X chromosomes is randomly switched off. If the chromosome carrying the normal gene gets turned off in a large proportion of cells, the carrier may not produce enough clotting factor.
Bleeding symptoms in female carriers are usually milder than in males with hemophilia, but not always. In rare cases, a woman with one hemophilia gene can bleed as seriously as a male with the condition. Carriers are also at higher risk for heavy bleeding after childbirth or surgery, including prolonged bleeding from the birth canal after delivery.
A Less Common Type: Factor XI Deficiency
A third form, sometimes called hemophilia C, is caused by mutations in the F11 gene, which makes clotting factor XI. Unlike hemophilia A and B, this type is not linked to the X chromosome. It follows an autosomal inheritance pattern, meaning it can affect males and females equally. Severe factor XI deficiency is autosomal recessive (requiring two mutated copies of the gene), but in some families, a single mutated copy is enough to cause problems. Factor XI deficiency is considerably rarer than the other two types and tends to produce milder bleeding, often noticeable only after surgery or dental procedures rather than spontaneously.
Acquired Hemophilia: Not Always Genetic
In a small number of cases, hemophilia isn’t inherited at all. Acquired hemophilia develops when a person’s immune system mistakenly produces antibodies that attack their own clotting factors, most commonly factor VIII. This autoimmune form typically appears in adults over 65, and about half of those affected have an underlying autoimmune disorder or cancer that triggers the immune response. A small percentage of cases, roughly 1 to 5 percent, occur in young women during pregnancy or shortly after delivery.
Acquired hemophilia can cause severe, unexpected bleeding in someone who has never had a bleeding problem before. Because there’s no family history and no childhood symptoms, it’s often diagnosed only after unusual bruising or bleeding prompts further testing.
How Severity Is Determined
The severity of hemophilia is directly tied to how much functional clotting factor your body produces. People with severe hemophilia have less than 1 percent of normal factor activity. They may bleed spontaneously into joints, muscles, and soft tissues, often starting in early childhood. Moderate hemophilia (1 to 5 percent of normal activity) causes prolonged bleeding after minor injuries, while mild hemophilia (5 to around 40 percent) may go undiagnosed for years, only surfacing after a major surgery or trauma.
The severity level generally stays consistent within a family because the same mutation is passed down. However, the experience can vary: two people with the same factor level may have different bleeding patterns depending on their activity level, body weight, and whether they develop inhibitors (antibodies against replacement clotting factor during treatment).