Hemophilia B, also known as Christmas disease, is a rare genetic bleeding disorder caused by low levels of the blood protein called factor 9. Factor 9 is a specialized protein necessary for blood clotting.
In contrast, hemophilia A is caused by the lack or insufficiency of clotting factor 8. It is 3 to 4 times more common than hemophilia B and is also less severe.
Without enough of the clotting factor, people with hemophilia bleed longer than those without the disease. Their bodies are unable to effectively stop the flow of blood from wounds.
Hemophilia B is considered mild, moderate, or severe depending on the level of factor 9 present and, relatedly, how easily bleeding occurs. People with mild hemophilia B typically experience bruising and bleeding only after injuries, trauma, surgery, and dental procedures.
People with moderate or severe hemophilia B may experience bleeding after minor injuries or even spontaneously, for no apparent reason. Spontaneous bleeding may occur internally into the joints and muscles as well as into the kidneys, stomach, intestines, and brain, among other organs, according to the National Organization for Rare Disorders (NORD).
Left untreated, hemophilia B may result in long-term joint problems and brain hemorrhage.
There is no cure for hemophilia B, but adequate treatment can stop bleeding episodes. Most people who have hemophilia B are able to lead a fairly normal life.
A drug approved by the U.S. Food and Drug Administration (FDA) in October 2024 has been shown to prevent or reduce the number of bleeding episodes by increasing clotting enzyme production. The FDA has approved Hympavzi, a medication that lowers the amount of anticoagulation proteins in the body, called tissue factor pathway inhibitors. When the level of these proteins is reduced, it allows the body to produce more thrombin, the enzyme that causes blood clotting to happen.
This medicine can be used to treat anyone age 12 or older who has hemophilia A without factor 8 inhibitors or hemophilia B without factor 9 inhibitors (neutralizing antibodies). The drug is dispensed weekly through a prefilled auto-injection pen.
Standard treatment for hemophilia B involves replacing the missing clotting factor so that the blood can clot properly. This is called factor 9 replacement therapy. The two main replacement therapies are plasma-derived factor concentrates and recombinant factor concentrates, which are infused into the bloodstream via a vein in the arm.
In both cases, infusions of the concentrates are done prophylactically, meaning they’re done on a regular basis to prevent bleeding episodes, according to the Centers for Disease Control and Prevention (CDC). However, if you have severe hemophilia B, you may also need to take a factor 9 concentrate before surgery or dental work, according to MedlinePlus.
People who have hemophilia usually learn to self-administer their replacement therapy at home. In fact the National Bleeding Disorders Foundation (NBDF) has self-infusion instructions for kids who are mature enough to learn how to infuse their own factor.
The cost of factor 9 replacement therapy is significant. The NBDF states that the average annual cost of clotting factor therapies for a person with severe hemophilia is roughly $300,000, and overall yearly medical expenses can be twice that.
Plasma-Derived Factor 9 Concentrates
Plasma-derived factor 9 concentrates are derived from human donations of blood or plasma.
The liquid part of blood, called plasma, contains clotting factors and other proteins, such as antibodies and albumin, according to the CDC. Albumin is a protein made by your liver to help keep fluid from leaking out of your blood vessels, according to MedlinePlus.
All donated blood or plasma go through tests for viruses. The plasma goes through multiple processes to separate it into components, such as clotting factors. The clotting factors are freeze-dried and treated to kill (or make inactive) any viruses found, according to the CDC.
Two plasma-derived factor 9 concentrates are available in the United States:
AlphaNine SD contains only blood factor 9 and no other factors.
Profilnine contains factor 9 along with factor 2, factor 10, and low levels of factor 7, according to DailyMed.
Recombinant Factor 9 Concentrates
About three-fourths of people with hemophilia take recombinant factor 9 concentrates, according to the NBDF. These products are developed in the lab using DNA technology. Recombinant factor 9 concentrates are not able to spread bloodborne viruses, because they are synthetic and not from humans, according to the CDC.
Available recombinant factor 9 concentrates include:
Alprolix
Benefix
Idelvion, which also contains albumin, according to the U.S. Food and Drug Administration (FDA)
Ixinity
Rebinyn
Rixubis
The Medical and Scientific Advisory Council (MASAC) of the NBDF recommends recombinant factor 9 concentrates over plasma-derived concentrates because they are safer.
About 3 in 100 people with hemophilia B develop an inhibitor — a type of antibody — to their treatment product. When this happens, the body stops accepting the factor concentrate as a normal part of the body, launching antibodies to destroy the foreign substances, according to the CDC. This can make it more difficult to stop a bleeding episode with the medication.
People with hemophilia are advised to get tested for inhibitors yearly so that serious health problems can be prevented. Inhibitors don’t necessarily cause symptoms, so a laboratory test is the only way to know whether a person has one.
Treatment for an inhibitor is complex and requires specialized medical expertise. It’s also costly: The NBDF states that a person with an inhibitor usually has medical expenses of more than $1 million per year.
In certain situations, drugs known as antifibrinolytics are used in addition to factor 9 replacement to assist with blood clotting and reduce blood loss.
Aminocaproic acid (Amicar) is a medication that prevents blood clots from breaking down. It is often used for bleeding in the mouth or after a tooth has been removed, because it blocks a substance found in the saliva that breaks down clots. It may also be recommended before dental procedures.
The drug can be taken orally as a pill or a liquid or can be infused through a vein. The MASAC notes in its treatment recommendations for hemophilia and other bleeding disorders that a dose of factor concentrate must be given first to form the clot, followed by aminocaproic acid to preserve the clot.
Tranexamic acid (Lysteda) similarly slows blood clots from being broken down. It’s typically prescribed to treat heavy menstrual bleeding in girls and women age 12 and older to reduce menstrual blood loss.
The CDC recommends that people with hemophilia B who are undergoing factor 9 replacement therapy do so with the help of a hemophilia treatment center (HTC). These are specialized care centers that provide patients with care and education to address all complications related to hemophilia.
According to the CDC, the medical staff at HTCs typically include:
Physicians, in particular hematologists (blood specialists)
Lab medical technologists
Pathologists (body tissue and fluids specialists)
Orthopedists (bones, joints, and muscles specialists)
Nurses
Social workers and other mental health professionals, such as psychologists
Physical therapists
Other healthcare providers specialized in the care of people with bleeding disorders
Research from the CDC shows that people who used an HTC for their care were 40 percent less likely to die of a hemophilia-related complication compared with those who didn’t go to an HTC. And those patients who used an HTC were also 40 percent less likely to be hospitalized for bleeding complications than those who didn’t.
The CDC has a directory to help you find an HTC near you.
Gene therapy eliminates the need for repeated treatment. With gene therapy, a one-time infusion is given that gives the body a working copy of the faulty gene that causes hemophilia. This working gene provides instructions for the body to produce the missing clotting factor.
In November 2022, the FDA approved the first gene therapy for hemophilia B: Hemgenix (etranacogene dezaparvovec). It’s approved for adults who are currently undergoing factor 9 replacement therapy, have a historical or current life-threatening hemorrhage, or have recurrent and serious spontaneous bleeding episodes, according to the FDA. However, per the prescribing information provided by drug maker CSL Behring, “Hemgenix is not intended for administration in women.”
Hemgenix is a one-time, single-dose gene therapy product. Given through an intravenous infusion, it contains a noninfectious viral vector, called an adeno-associated virus, carrying a gene for factor 9. It expresses in the liver to produce the protein and increase blood levels of factor 9.
According to the FDA, the safety and effectiveness of Hemgenix were evaluated in two studies of 57 adult men ages 18 to 75 with severe or moderately severe Hemophilia B. In one study, with 54 participants, researchers found that subjects who took the gene therapy had:
Increases in factor 9 in their blood
A reduction in routine factor 9 replacement therapy
A 54 percent reduction in annualized bleeding rate compared with baseline
Adverse reactions to the therapy included:
Increases in liver enzymes
Headache
Mild infusion-related reactions
Flu-like symptoms
The list price of Hemgenix is $3.5 million per treatment per individual, making it the most expensive drug in the world. Thus far, the drugmaker has presented data showing Hemgenix’s effects endure for two years after infusion. Future research will determine how long its efficacy persists over time.
The Takeaway
Hemophilia B is caused by a lack of clotting factor 9.
The standard treatment is factor 9 replacement therapy.
Newer treatments include medicine to increase the level of clotting enzymes in the blood, and gene therapy, which provides a working copy of the faulty gene that causes hemophilia.
Hemophilia treatment centers can provide support and education for people who have hemophilia.
