Hemophilia B

Hemophilia B is a rare genetic bleeding disorder that impairs the blood’s ability to clot properly.

It is caused by a mutation in the F9 gene, located on the X chromosome, resulting in a deficiency in a blood-clotting protein called factor IX (FIX).

This type of hemophilia accounts for 15% to 20% of all hemophilia cases in the U.S. In contrast, hemophilia A accounts for about 80% of cases and is caused by a mutation in the F8 gene that results in a deficiency of clotting factor VIII.

Unlike some other bleeding disorders — like von Willebrand disease — which are equally common among men and women, hemophilia B is more common in men, occurring in around 1 in 25,000 male births.

Hemophilia B genetics and inheritance

Hemophilia B inheritance follows an X-linked recessive pattern. Because boys have only one X chromosome, if they inherit a mutated F9 gene, they will have hemophilia B.

Girls receive two X chromosomes, one from each parent. If a girl inherits one X chromosome with a faulty F9 gene and one X chromosome with a healthy F9 gene, she is considered a carrier.

Carriers do not usually have symptoms, but can pass the affected F9 gene on to their children. In certain cases, female carriers may have hemophilia and present similar symptoms to men, particularly when their factor IX levels are low.

In some cases, hemophilia B may occur without any family history of the condition, due to spontaneous mutations in the F9 gene.

Leyden inheritance

Hemophilia B Leyden is a subtype of hemophilia B and accounts for approximately 3% of all type B cases.

The mutations causing this subtype of hemophilia B occur in the promoter region of the F9 gene, a specific area in the DNA code that controls when a gene is turned on (activated) or off (inactivated).

Hormonal changes during puberty can activate this promoter region to a certain degree, increasing FIX levels, which can decrease bleeding episodes.

People with this subtype often have somewhat normal FIX levels by midlife and may no longer need hemophilia B medications.

Hemophilia B symptoms

Hemophilia B symptoms include spontaneous bleeding episodes, along with joint and muscle bleeding.

Depending on FIX activity levels, hemophilia B can be considered mild, moderate, or severe.

Mild

People with mild hemophilia B typically have FIX activity levels ranging from 5% to 40% of normal. This means they may remain undiagnosed until a surgical procedure results in prolonged bleeding, and there may be many years between episodes.

In mild hemophilia B, significant trauma or injury, as well as surgery or dental procedures, may cause bruising and bleeding.

These bleeding episodes usually last longer and are more severe compared with those in people without hemophilia. Spontaneous bleeding is relatively rare in mild hemophilia B.

Moderate

People with moderate hemophilia B typically have FIX activity levels ranging from 1% to 5% of normal. They are usually diagnosed by 5 or 6 years of age, and the frequency of spontaneous bleeding episodes is highly variable.

In moderate hemophilia B, bleeding may occur following minor injuries or without an apparent cause, known as spontaneous bleeding. Prolonged bleeding may happen after trauma, surgeries, or dental procedures.

Symptoms may include:

• easy bruising
• prolonged nosebleeds
• hematomas (blood-filled bumps under the skin) after minor injuries
• joint and muscle bleeds that cause complications such as pain and immobility

Severe

People with the severe form of hemophilia B typically have FIX activity levels of less than 1% of normal. Severe forms are usually identified early during infancy or childhood.

Severe hemophilia B poses the highest risk of spontaneous and severe bleeding triggered by even minor trauma.

Symptoms may include:

• internal bleeding in the joints, muscles, or other internal organs
• significant pain, swelling, and potential long-term joint damage
• bleeds in the gastrointestinal tract

Bleeding into the brain, although rare, can also occur, leading to symptoms of severe headache, vomiting, seizures, and neurological changes. It may potentially be life-threatening.

Complications

Hemophilia B can also lead to several complications.

These can include:

• lasting damage and ongoing pain in joints due to repeated joint bleeds
• anemia and blood pressure changes due to bleeding in large muscles, such as the hips and thighs
• compartment syndrome due to bleeding occurring in confined muscles, such as those in the forearm and calf

People with hemophilia B are also at higher risk of developing osteopenia and osteoporosis, two conditions marked by the loss of bone tissue.

Hemophilia B treatment

Treatment includes factor replacement therapy to control and prevent bleeds, along with gene therapy.

The standard approach to prevent and manage bleeding episodes in a person with hemophilia B is replacement therapies that provide functional FIX protein. Commonly used treatments contain recombinant factor IX (rFIX), a lab-made version of the missing clotting factor.

Replacement therapy can be used on demand to manage acute bleeding episodes or serve as a regular preventive measure (prophylaxis) to reduce the risk of bleeding. Prophylaxis is typically advised for the more severe forms of the disease.

Non-factor therapies may also be used as an alternative to prevent or reduce the frequency of bleeding episodes in people with hemophilia B. Unlike factor replacement therapies, these treatments don’t rely on replacing the missing or faulty clotting factor to promote blood clotting.

Additionally, some people may receive antifibrinolytics, which are medications that help slow the body’s natural process of breaking down blood clots.

Several experimental therapies are being tested in clinical trials to provide long-term solutions for hemophilia B, including gene therapies that aim to boost factor IX levels and reduce or eliminate the need for regular infusions.

Scientists are also exploring gene-editing technologies, such as CRISPR/Cas9, to correct genetic mutations causing hemophilia B.

Gene therapy

Researchers have developed hemophilia B gene therapies that introduce a healthy copy of the F9 gene into people with the condition.

These are given via a one-time intravenous (into-the-vein) infusion that is expected to help keep bleeding in check over the long term.

People living with hemophilia B are encouraged to stay informed about treatment developments and discuss any concerns with their healthcare providers.

Hemophilia B diagnosis

Doctors diagnose Hemophilia B through a combination of clinical evaluation, medical history, and laboratory tests.

A healthcare provider will review your medical history and ask about any symptoms of bleeding or a family history of bleeding disorders. A physical exam will look for signs such as bruises, swollen joints, or external bleeding.

Lab tests are crucial for a definitive diagnosis of hemophilia B and include blood tests to assess clotting function and clotting factor activity levels, as well as genetic testing. Specific tests include:

• A factor IX assay, which measures the activity level of FIX in the blood, can be used to confirm the diagnosis of hemophilia B and determine the severity of the disease.
• Blood tests can be used to assess clotting ability and overall blood health, including the activated partial thromboplastin time test, which measures the time it takes for blood to clot.
• Genetic testing can identify the specific gene mutation responsible for hemophilia B.

Living with hemophilia B

When you are living with hemophilia B, you can aim to manage your symptoms with treatment and lifestyle changes.

• Set up regular appointments at a specialized hemophilia treatment center. There are more than 140 hemophilia treatment centers located in the U.S., and at least 25 treatment centers are located in Canada.
• Learn how to self-administer the factor replacement therapy at home, which can offer more control and independence in managing the condition.
• Write an emergency treatment plan, including contact information for the local hemophilia treatment center, and carry a medical ID that indicates you have hemophilia B.
• Learn how to treat the disease in an emergency, such as applying pressure to the site, calling for emergency help, and, if trained, administering FIX replacement therapy.
• Avoid high-impact activities and take safety precautions to reduce the risk of bleeding.
• Maintain joint health with regular exercise, such as swimming and low-impact sports, as well as physical therapy.
• Stay current with vaccinations, especially for hepatitis A and B, to protect the liver, which may be affected by hemophilia treatments.
• Eat a balanced diet and maintain a healthy weight to reduce joint strain and improve overall health.
• Avoid excessive alcohol and non-prescription medications that can interfere with blood clotting.

Seek emotional and mental health support as needed by connecting with support groups and mental health counselors or talking with family and friends.