Haemophilia B without inhibitors

Haemophilia B, also known as Christmas disease, is an inherited bleeding disorder caused by a deficiency in clotting factor IX. While it predominantly affects males due to its X-linked inheritance pattern, effective treatment allows most people with this condition to lead normal, active lives.

Table of contents

• What is haemophilia B?
• Causes and inheritance
• Signs and symptoms
• Severity levels
• Diagnosis and testing
• Treatment options
• Living with haemophilia B

What is haemophilia B?

Haemophilia B is a hereditary bleeding disorder caused by a lack of blood clotting factor IX (also called factor 9). Without enough factor IX, the blood cannot clot properly to control bleeding^[3]. The condition is also known as Christmas disease, named after Stephen Christmas, the first person diagnosed with this disorder in 1952^[2].

When you bleed, a series of reactions take place in the body that helps blood clots form. This process is called the coagulation cascade. It involves as many as 20 different special proteins called coagulation, or clotting factors. You may have a higher chance of excess bleeding if one or more of these factors are missing or are not functioning like they should^[3].

Haemophilia B is the second most prevalent form of haemophilia, accounting for about 20% of hemophilia cases^[8]. It is about three to four times less common than haemophilia A^[4]. In the United States, haemophilia B occurs in about 1 in 19,000 male births^[7].

Christmas disease, Factor IX deficiency

Causes and inheritance

Haemophilia B is caused by a defect in the F9 gene, which provides instructions for making clotting factor IX. The genetic defect can occur either through X-linked inheritance or a spontaneous de novo mutation^[2].

The condition is caused by an inherited X-linked recessive trait, with the variant gene located on the X chromosome^[3]. Here’s how this inheritance pattern works:

Females have two copies of the X chromosome. If the factor IX gene on one chromosome does not work, the gene on the other chromosome can do the job of making enough factor IX. Males have only one X chromosome. If the factor IX gene is missing on a boy’s X chromosome, he will have haemophilia B. For this reason, most people with haemophilia B are male^[3].

If a woman has a variant factor IX gene, she is considered a carrier. This means the variant gene can be passed down to her children. Boys born to such women have a 50% chance of having haemophilia B. Their daughters have a 50% chance of being a carrier. All female children of men with haemophilia carry the variant gene, whereas male children do not^[3].

Approximately 30% of heterozygous females have factor IX clotting activity lower than 40% and are at risk for bleeding. As in males, bleeding severity generally correlates with factor IX levels^[5].

Signs and symptoms

Haemophilia B is characterized by prolonged oozing after injuries, tooth extractions, or surgery, and delayed or recurrent bleeding prior to complete wound healing^[5]. The severity of symptoms can vary depending on the level of factor IX in the blood.

Prolonged bleeding is the main symptom. It is often first seen when an infant is circumcised. Other bleeding problems usually show up when the infant starts crawling and walking. Mild cases may go unnoticed until later in life. Symptoms may first occur after surgery or injury^[3].

Common signs of haemophilia include^[4]:

• Bleeding into the joints, which can cause swelling and pain or tightness in the joints; it often affects the knees, elbows, and ankles
• Bleeding into the skin (which is bruising) or muscle and soft tissue causing a build-up of blood in the area (called a hematoma)
• Bleeding of the mouth and gums, and bleeding that is hard to stop after losing a tooth
• Bleeding after circumcision
• Bleeding after having shots, such as vaccinations
• Blood in the urine or stool
• Frequent and hard-to-stop nosebleeds
• Bleeding that starts without cause

Internal bleeding may occur anywhere. Very rarely, severe haemophilia causes bleeding into the brain. This is a life-threatening condition. Symptoms are persistent headaches, double vision, or feeling very tired. If you have haemophilia and have these symptoms, get medical care right away^[6].

Severity levels

Healthcare providers classify haemophilia as being severe, moderate, or mild. They base the classification on the number of clotting factors in your blood^[6]. The severity of haemophilia that a person has is determined by the amount of factor in the blood. The lower the amount of the factor, the more likely it is that bleeding will occur^[4].

Severe haemophilia B: People with less than 1% normal factor (less than 0.01 IU/mL) are considered to have severe haemophilia^[8]. This form is usually diagnosed during the first two years of life. Without prophylactic treatment, individuals may average up to two to five spontaneous bleeding episodes each month, including spontaneous joint or muscle bleeds, and prolonged bleeding or excessive pain and swelling from minor injuries, surgery, and tooth extractions^[5].

Moderate haemophilia B: People with 1-5% normal factor (0.01-0.05 IU/mL) are considered to have moderately severe haemophilia^[8]. Individuals have less frequent spontaneous bleeding, although it varies between individuals; however, individuals with moderate haemophilia B do have prolonged or delayed oozing after relatively minor trauma and are usually diagnosed before age five to six years. The frequency of bleeding episodes varies from once a month to once a year^[5].

Mild haemophilia B: People with more than 5% but no more than 40% normal factor (greater than 0.05 to 0.40 IU/mL) are considered to have mild haemophilia^[8]. Individuals generally do not have spontaneous bleeding episodes; however, without pre- and postoperative treatment, abnormal bleeding occurs with surgery or tooth extractions. The frequency of bleeding may vary from once a year to once every ten years. Individuals with mild haemophilia B are often not diagnosed until later in life^[5].

Diagnosis and testing

The diagnosis of haemophilia B is established in individuals with low factor IX clotting activity. If you are the first person in your family to have a suspected bleeding disorder, your healthcare provider will order a series of tests called a coagulation study^[3].

Tests to diagnose haemophilia B include^[3]:

• Partial thromboplastin time (PTT)
• Prothrombin time (PT)
• Serum factor IX activity

Identification of a hemizygous F9 pathogenic variant by molecular genetic testing confirms the diagnosis in a male patient. Identification of a heterozygous F9 pathogenic variant by molecular genetic testing confirms the diagnosis in a female patient^[5]. Once the specific variant has been identified, other people in your family will need tests to diagnose the disorder^[3].

Treatment options

Treatment includes replacing the missing clotting factor. The standard way to treat haemophilia B is to replace the missing blood clotting factor so that the blood can clot properly^[13]. With treatment, most people with haemophilia B are able to lead a fairly normal life^[3].

Factor replacement therapy

The most common treatment for haemophilia B is called replacement therapy. Concentrates of clotting factor IX are the foundation of this treatment for haemophilia B and are administered as an infusion to help replace the clotting factor that’s missing or low in the blood^[12]. People with haemophilia can learn how to perform infusions themselves so that they can stop bleeding episodes and, by performing the infusions on a regular basis, can even prevent most bleeding episodes^[13].

There are two main types of clotting factor concentrates available^[13]:

Recombinant factor concentrates: These are lab-made clotting factors genetically engineered using DNA technology. They do not come from human plasma and do not contain any plasma or albumin, and therefore, cannot spread any bloodborne viruses^[13]. Commercially prepared factor concentrates are treated to remove or inactivate bloodborne viruses^[13].

Plasma-derived factor concentrates: These are made from human plasma proteins. All blood and parts of blood, such as plasma, are routinely tested for viruses. The plasma is collected from many people, and then it goes through several processes to separate it into components, such as clotting factors. The clotting proteins are then made into a freeze-dried product, which is tested and treated to kill any potential viruses before it is packaged for use^[13].

Treatment approaches

Healthcare providers typically prescribe treatment products for episodic care or prophylactic care^[13]:

Prophylactic (preventive) treatment: For people with severe haemophilia B and those with moderate or mild haemophilia B and frequent bleeding, prophylactic treatment with factor IX concentrate infusions to maintain factor IX clotting activity higher than 1% or as needed to prevent bleeding and allow normal activity improves outcomes and prevents chronic joint disease^[9]. For people with haemophilia B, most preventative treatment involves infusions every 7 to 14 days. The general goal of prophylaxis is to maintain the factor level above 1%, especially for severe haemophilia B patients^[12].

On-demand (episodic) treatment: This is used to stop a patient’s bleeding episodes. Infusions are given as soon as a bleed starts or after an injury^[13].

How much you get depends on the severity of bleeding, the site of bleeding, and your weight and height. To prevent a bleeding crisis, people with haemophilia and their families can be taught to give factor IX concentrates at home at the first signs of bleeding^[3].

Treatment centers

Good quality medical care from healthcare providers who know a lot about the disorder can help people with haemophilia prevent some serious problems. This type of specialty care is at a comprehensive hemophilia treatment center (HTC). An HTC provides patients with the care and education to address all issues related to the disorder. The team consists of physicians (hematologists or blood specialists), nurses, social workers, physical therapists, and other healthcare providers who are specialized in the care of people with bleeding disorders^[13].

Home treatment

Home treatment has several advantages^[12]:

• Treatment can be given more quickly when bleeding happens
• Early treatment lowers the risk of complications
• Fewer visits to the healthcare provider or emergency room are needed
• Home treatment costs less than treatment in a medical care setting
• Home treatment helps children accept treatment and take responsibility for their own health

Living with haemophilia B

Treatment is so effective that people who have haemophilia generally live just as long as people who don’t have the condition^[15]. By sticking to a treatment plan, staying active, and connecting with others, people with haemophilia B can lead a full and healthy life^[15].

Stay active and safe

Exercise has lots of physical and mental benefits, especially for children and young adults. Choose low-impact activities, such as swimming, walking, or yoga. It’s best to steer clear of contact sports such as football and hockey, but others, such as baseball or tennis, can be good options. Talk to a physical therapist at the hemophilia treatment center before starting a program, and always take proper precautions, such as wearing a mouth guard and helmet^[15].

Protect joints after injury

If you get injured, remember the acronym PRICE^[15]:

• Protect the area by limiting its movement (e.g., wear a brace)
• Rest the area to limit swelling
• Ice the area with a cold pack to reduce pain
• Compress the area to reduce bleeding and swelling
• Elevate the area, especially within the first 48 hours of injury, to reduce bleeding and swelling

Regular check-ups and dental care

You should have regular checkups with a hematologist. If you have severe haemophilia, you may need routine treatment. Every 6 to 12 months or so, depending on your needs, you should meet with your providers at the hemophilia treatment center you go to. You can discuss treatment and whether you have enough supplies on hand in case of an emergency^[15].

Because the complications from teeth and gum problems can cause bleeding, they may be more serious for people with haemophilia B. That’s why it’s important to get regular dental cleanings^[15]. If you have severe forms of the disease, you may need to take factor IX concentrate before surgery or certain types of dental work^[3].

Vaccinations

You should get the hepatitis B vaccine. People with haemophilia are more likely to get hepatitis B because they may receive blood products^[3].

Emotional support

Living with haemophilia can be restrictive, and patients may not be able to attend or perform certain activities due to the increased risk of bleeding. This inability can have negative effects on psychological health and cause feelings of sadness, anxiety, or anger^[16]. You can ease the stress of illness by joining a haemophilia support group. Sharing with others who have common experiences and problems can help you not feel alone^[3].