Hemophilia B

Related Terms

Bleeding, bruising, Christmas disease, coagulation, factor IX, factor IX hemophilia, haemophilia, haemophilia B, hemophilia, hematuria, hematochezia, hemorrhage, X-linked.

Background

Hemophilia B, also called factor IX deficiency, is a blood clotting disorder caused by a deficiency of a clotting protein called factor IX. Blood clots are clumps of different types of blood cells and clotting factors that stop bleeding after an injury to allow wound healing. People with hemophilia, including factor IX deficiency, do not form clots properly. This leads to bleeding that can range from mild to severe. Hemophilia B is the second most common type of hemophilia. Hemophilia B is sometimes called Christmas disease after Stephen Christmas, who was the first patient described with this disease. The first report of this deficiency was published during the Christmas season of 1952.
The process of blood clotting is called coagulation, or hemostasis. When a blood vessel (vein or artery) becomes injured, it narrows to slow blood flow so that clotting can begin. At the same time, the blood that has leaked outside of the injured blood vessel presses against the vessel to help prevent further blood loss. Blood cells called platelets are activated to move toward the site of injury. Once platelets reach the site of injury, a series of reactions facilitated by enzymes called "coagulation factors" lead to the activation of a protein called thrombin. This protein converts a blood clotting factor called fibrinogen into long strands that form a net around the platelets and blood cells. This net helps trap more platelets to form a blood clot. The blood clot, also called a thrombus, is a temporary plug to control bleeding in order to allow wound healing.
Once the platelets are clumped together, they change in shape from round to spiny so that they stick to the wall of the broken blood vessel. Internal blood clots appear as bruises under the skin while others are visible on the surface of the skin as scabs. Once the blood vessel is healed, other blood factors are released to destroy the clot and dissolve it into the blood.
Symptoms of hemophilia B usually appear during infancy or early childhood. Due to an inability to properly form clots, patients experience prolonged bleeding in response to injuries, such as scrapes, bruises, cuts, or nosebleeds, as well as after surgical procedures. Some patients may experience pain and swelling in their joints, including the knees, elbows, ankles, shoulders, and hips caused by internal bleeding in the affected joint. When a person with hemophilia B is injured, he or she does not bleed harder or faster than a person without hemophilia, but rather he or she bleeds for a longer time. Small cuts or surface bruises are usually not a problem, but more-traumatic injuries may result in serious problems, such as hemorrhage, anemia, and "bleeding episodes."
Hemophilia B is usually inherited, or passed down, from parents. Because hemophilia can be inherited, the risk of disease increases in closely related families. In about 30% of cases, however, there is no family history of the disorder and the condition is the result of a spontaneous gene mutation. Approximately 1 in 25,000 people worldwide are born with hemophilia B. All races are affected equally.
Currently, there is no known cure for hemophilia B. If treated properly, however, patients can live normal, healthy lives. Patients may receive clotting factor replacement therapy to restore the function of the missing clotting factor IX.

Signs and symptoms

Symptoms of hemophilia B usually appear during infancy or early childhood. Due to an inability to properly form blood clots, patients with hemophilia experience prolonged bleeding in response to injuries, such as scrapes and cuts or nosebleeds. Patients with hemophilia may experience excessive bleeding after undergoing surgical or dental procedures and may be more susceptible to bruising.
The severity of symptoms can vary with hemophilia B. Severe forms of hemophilia B become obvious during infancy. Hemorrhaging or uncontrolled bleeding is the hallmark of the disease and often occurs when an infant is circumcised. Additional bleeding episodes occur when the infant starts to crawl and walk. Internal bleeding may occur anywhere and bleeding into joints is common.
Some patients have blood in their urine (hematuria) or stool (hematochezia). This is usually a result of internal bleeding from an organ, such as the kidney, bladder, intestines, or stomach. Spontaneous bleeding and gastrointestinal tract and urinary tract hemorrhaging may occur.
The severity of symptoms in patients with hemophilia may vary, with some patients experiencing more difficulty in forming clots than others. Patients with severe hemophilia may take days or weeks to heal from an injury. In patients who have mild hemophilia, prolonged bleeding may result only after very severe injuries or surgery, and thus may not become apparent or problematic until adulthood.

Diagnosis

Blood tests: If patients experience symptoms of hemophilia B, such as prolonged bleeding or excessive bruising, doctors may diagnose the condition by performing a blood test. A doctor will remove, or draw, a small amount of blood and check for the presence of clotting factor IX. If it is missing or found at very low levels, a diagnosis of hemophilia B can be made.
Additional tests can be performed on blood samples in the laboratory to measure whether clotting is abnormally slow. This is done by simply observing how long it takes for drawn blood to form a clot. Blood tests may also be performed on a developing fetus or after birth.
Another clotting factor that might be measured in the blood in order to make an accurate diagnosis is fibrinogen, which is found at abnormal levels in patients with hemophilia B.
Partial thromboplastin time (PTT) is a blood test that measures how long it takes for blood to clot. PTT is prolonged in patients with hemophilia B.
Genetic testing: Mutations in clotting factor genes are known to cause hemophilia B. Mutations that may occur in clotting factor genes include inversions (a reverse in the gene orientation) and partial or complete gene deletions (missing genes). Genetic tests can be used to check for these mutations, to diagnose hemophilia B, and to identify carriers of the mutation. These tests may be used to confirm a diagnosis if there is a family history of hemophilia B or if symptoms are present. Prenatal testing for hemophilia B is under development.

Complications

Anemia: Anemia is a condition caused by not having enough red blood cells. Anemia may also occur when the number of red blood cells is normal but they don't contain enough hemoglobin. Hemoglobin is a protein that gives blood its red color and carries oxygen in the bloodstream. People with anemia do not get enough oxygen delivered to their tissues by the blood. Without oxygen, the organs and tissues cannot work properly. One cause of anemia is excessive blood loss, which is common in patients with hemophilia B.
Brain bleeding: If a patient with hemophilia experiences a head injury, even just a simple bump, internal bleeding in the brain may occur. In some people with hemophilia B, bleeding into the brain may occur spontaneously. Brain bleeding may result in headaches, fatigue, weakness, vomiting, or seizures, and may be life-threatening.
Excessive bleeding: If external bleeding is not stopped in severe cases of hemophilia, excessive blood loss may lead to death. This is most likely to occur in situations in which appropriate treatment is not available.
Hepatitis C virus (HCV) or HIV: In the past, donated blood that was used to obtain replacement clotting factors was not commonly screened. In many cases, the blood was contaminated with the hepatitis C virus (HCV) or HIV. Many patients with hemophilia who received replacement clotting factor treatment were therefore at increased risk for HCV or HIV infection. Today, the risk of getting these diseases from blood transfusions is low because laboratories routinely screen banked blood for these and other infections before transfusions begin.
Joint bleeding: Some patients with hemophilia B may experience pain and swelling in their joints, including in the knees, elbows, ankles, shoulders, and hips. This is caused by internal bleeding in the joints, which may occur without any obvious injury. In severe cases, joint bleeding may be prolonged and can lead to permanent joint damage. Some patients may have difficulty walking or moving due to the pain and swelling. Chronic, or long term, joint deformities may be managed by an orthopedic specialist.
Thrombosis: Treatment with clotting factors may cause excessive clotting, which results in thrombosis. Thrombosis is the formation of a clot, or thrombus, inside a blood vessel that can obstruct the flow of blood through the circulatory system. Thrombosis may occur following prolonged treatment with factor IX, especially in patients with liver disease. If prolonged factor IX infusion is necessary, a small amount of heparin (a blood thinner that prevents clotting) is often added to prevent excessive clotting.

Treatment

General: Currently, there is no known cure for hemophilia B. Treatment generally focuses on managing the symptoms and preventing complications. For patients with mild forms of hemophilia B, minor cuts and scrapes can usually be treated by cleaning the cut, applying pressure, and putting on a bandage. However, more severe forms may require drugs or clotting factor replacement therapy. Patients should tell their healthcare providers about any prescription or over-the-counter drugs, herbs, or supplements they are taking because they may interact with treatment.
Activity restriction: People with hemophilia B should avoid contact sports and other activities that could result in injury. Protective gear is available for children with hemophilia to help reduce the incidence of injury that could result in organ rupture or bleeding episodes. These include knee and elbow pads, helmets, and padded shorts.
Blood transfusions: Patients who suffer from severe bleeding may receive blood transfusions with donated blood to help to restore the lost blood.
Clotting factor replacement therapy: The standard treatment for hemophilia B is infusion of factor IX concentrates to replace the defective clotting factor. This type of therapy effectively reduces the symptoms of hemophilia B. Replacement clotting factors may be obtained from donated blood or can be generated in a laboratory. After proper training, parents or older patients may be able to administer the replacement factor at home, making it more convenient to obtain treatment. The amount infused depends on the severity and site of the bleeding, and the weight of the patient.
Sources of factor IX may include prothrombin complex, which contains the inactive vitamin K-dependent clotting factors; activated prothrombin complex, which contains the active vitamin K-dependent clotting factors; or fresh frozen plasma, which does not contain sufficient levels of factor IX for those with severe hemophilia.
To prevent a bleeding crisis, people with hemophilia and their families can be taught to administer factor IX concentrates at home at the first signs of bleeding. People with severe forms of the disease may need to receive clotting therapy on a regular basis, often two to three times per week. Patients with less severe hemophilia may need to receive therapy only before an activity that may cause bleeding, such as surgery. Depending on the severity of the disease, factor IX concentrate may be given prior to dental extractions and surgery to prevent bleeding. Because some patients may need to receive infusions of clotting factor regularly over the course of their lives, clotting factor replacement therapy may be very expensive.
In rare instances, people with hemophilia B can develop an inhibitor, or a resistance, to standard clotting factor treatment. Only about 3 to 5% of patients with severe hemophilia develop an inhibitor. However, allergic reactions to clotting factor have occurred in some patients with hemophilia B inhibitors. In these patients, the immune system produces antibodies that attack clotting factor proteins. Antibodies are a component of the immune system that normally attack foreign invaders, such as viruses or bacteria, to help destroy them. For unknown reasons, however, people with hemophilia B may produce antibodies that impair the function of clotting factors. In patients who produce these abnormal antibodies, clotting factor replacement therapy may not be effective.
Drugs to avoid: Aspirin, warfarin, and heparin are blood thinners that prevent clots from forming and should usually not be used by patients with hemophilia B.
Gene therapy: Studies are being done to use gene therapy to treat people with hemophilia B. If successful, the body would be able to make its own properly functioning factor IX instead of having to rely on clotting factor replacement therapy.
Hepatitis B vaccine: The hepatitis B vaccine is recommended for individuals with hemophilia B because they are at increased risk of developing hepatitis due to exposure to blood products.
Vitamin K: Low levels of vitamin K may lead to increased bleeding, especially in infants. That is why newborns typically receive injections of vitamin K shortly after birth. Vitamin K is found in green leafy vegetables, such as spinach, broccoli, asparagus, watercress, and cabbage, as well as in cauliflower, green peas, beans, olives, canola, soybeans, meat, cereals, and dairy products. Patients should talk to their healthcare providers or pharmacists before taking supplements containing vitamin K.
Patients who are already receiving coagulation therapy should not drastically change their eating habits unless they first consult their healthcare providers. Significant changes in vitamin K consumption may have an impact on the effectiveness of treatment.

Integrative therapies

Note: Currently, there is insufficient evidence available on the safety and effectiveness of integrative therapies for the prevention or treatment of hemophilia B. The therapies listed below have been studied for the prevention or treatment of bleeding or hemorrhaging. They should be used only under the supervision of a qualified healthcare provider and should not be used to replace other proven therapies or preventive measures.
Good scientific evidence:
Rhubarb: Rhubarb has been used in traditional Chinese medicine for many gastrointestinal (digestive tract) disorders, including upper gastrointestinal bleeding. Preliminary evidence suggests that rhubarb may help reduce upper gastrointestinal bleeding. Higher quality studies are needed to confirm this hypothesis. While the use of rhubarb to treat hemophilia has not been well studied, it may be effective in treating the disease based on symptoms that patients exhibit.
Avoid if allergic or sensitive to rhubarb. Avoid using rhubarb for more than two weeks because it may induce tolerance in the colon, melanosis coli (pigmentation disorder in the wall of the colon), laxative dependence, problems with muscle tone in the colon, and substantial loss of electrolytes. Avoid using rhubarb in patients with atony, colitis, Crohn's disease, dehydration with electrolyte depletion, diarrhea, hemorrhoids, insufficient liver function, intestinal obstruction or ileus, irritable bowel syndrome, menstruation, pre-eclampsia, renal disorders, ulcerative colitis, and urinary problems. Avoid handling rhubarb leaves because they may cause a skin rash. Avoid rhubarb in children under age 12 due to the potential for water depletion (dehydration). Use cautiously with bleeding disorders, cardiac conditions, coagulation therapy, constipation, history of kidney stones, or thin or brittle bones. Use cautiously if taking antipsychotic drugs or oral drugs, herbs, or supplements (including calcium, iron, and zinc). Avoid if pregnant or breastfeeding.
Unclear or conflicting scientific evidence:
Bellis perennis: Bellis perennis is a common European species of daisy that has been used traditionally for treating wounds. Although homeopathic dosing is Generally Recognized as Safe (GRAS) by the U.S. Food and Drug Administration (FDA), there is a lack of well-designed clinical trials to support claims for efficacy related to the use of Bellis perennis. More research is needed in this area. Avoid if allergic or sensitive to Bellis perennis, its constituents, or other plants of the Asteraceae/Compositae family, such as ragweed, chrysanthemum, marigold, and dandelion. Use cautiously if taking anticoagulants or with bleeding disorders. Use cautiously if at risk for coagulation disorders such as strokes or blood clots. Use cautiously with anemia. Avoid use in children at traditional herbal doses because of the possibility of growth stunting. Avoid if pregnant or breastfeeding because of the possibility of growth retardation in the fetus and infant.
Hypnosis: There is inconclusive evidence from early research of hypnosis therapy for hemophilia. Additional study is needed before a firm conclusion can be drawn. Use cautiously with mental illnesses such as psychosis/schizophrenia, manic depression, multiple personality disorder, or dissociative disorders. Use cautiously with seizure disorders. Reported side effects include changes in skin temperature, heart rate, intestinal secretions, immune response, decreased blood pressure and brain wave patterns, disturbing memories, and false memories.
Vitamin K: Vitamin K is found in green leafy vegetables, such as spinach, broccoli, asparagus, watercress, and cabbage, as well as in cauliflower, green peas, beans, olives, canola, soybeans, meat, cereals, and dairy products. Vitamin K deficiency in infants may lead to hemorrhagic disease of the newborn, also known as vitamin K deficiency bleeding (VKDB). Although almost half of newborns may have some degree of vitamin K deficiency, serious hemorrhagic disease is rare. Because vitamin K given by injection has been shown to prevent VKBD in newborns and young infants, the American Academy of Pediatrics recommends administering a single intramuscular injection of vitamin K to all newborns. Oral dosing is not considered adequate as prevention, particularly in breastfeeding infants. Initial concerns of cancer risk were never proven and are generally not considered clinically relevant. In cases of true VKDB, bleeding may occur at injection sites, at the umbilicus, or in the gastrointestinal tract. Life-threatening bleeding into the head (intracranial) or in the area behind the lower abdomen (retroperitoneal) may also occur. Evaluation by a physician is imperative.

Prevention

General: There are currently no known ways to prevent hemophilia B. However, genetic counseling is available for prospective parents with family histories of hemophilia.
Genetic testing and counseling: Individuals from high-risk populations, or those with family histories of hemophilia B, may meet with genetic counselors to determine whether they carry a genetic mutation linked to the disease. Carriers can be determined through detailed family histories or by genetic testing. Known carriers may undergo genetic counseling before they conceive a child. Genetic counselors can explain the options and the associated, sometimes serious, risks of various prenatal tests, such as amniocentesis or chorionic villus sampling (CVS). Patients should discuss the potential health benefits and risks associated with these procedures before making any medical decisions.
During amniocentesis, a long, thin needle is inserted through the abdominal wall into the uterus and a small amount of amniotic fluid is removed from the sac surrounding the fetus. The fluid is then analyzed for a mutated gene. This test is performed after 15 weeks of pregnancy. Some experts estimate that the risk of miscarriage ranges from one out of 200 to one out of 400 patients. The rate of miscarriage is highest when the procedure is done early in pregnancy, before the two layers of fetal membranes have sealed. A woman's particular risk depends in large part on the skill and experience of the doctor performing the procedure. Some patients may experience minor complications, such as cramping, leaking fluid, or irritation where the needle was inserted.
During CVS, a small piece of tissue (chorionic villi) is removed from the placenta during early pregnancy. Depending on where the placenta is located, CVS can be performed through the cervix or through the abdomen. The tissue sample is then analyzed for a mutated gene. This procedure may be performed between the ninth and 14th week of pregnancy. The risks of infection or fetal damage are slightly higher than those of amniocentesis. Miscarriage occurs in about two out of 100 women who undergo this procedure. Factors that further increase the risk of CVS include having the procedure three or more times and having a fetus that is smaller than normal for gestational age. The physician's skill and experience also play an important role.
Before and after genetic testing, it is recommended that people meet with genetic counselors. These professionals can help patients understand the risks of having a child with hemophilia B. A genetic counselor can also explain the different types of genetic tests, including potential risks and benefits. These counselors can also help patients understand and interpret test results.

Author information

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

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Causes

General: Hemophilia is caused by defects, or mutations, in genes that make proteins called clotting factors. These proteins function in coagulation, which is a step in the clotting process when a protein net is formed around torn blood vessels to stop the bleeding. These clotting factors help cells in the blood called platelets stick together at the site of an injury.
Genetic: Patients with hemophilia B have mutations in the F9 gene, which contains instructions for making clotting factor IX. When this clotting factor is not properly made, individuals cannot form effective blood clots. About 70% of hemophilia cases are inherited, meaning that a defective clotting factor gene is transmitted from a parent to a child. However, about 30% of cases are not inherited. These cases are caused by a spontaneous genetic mutation in the egg or sperm or during embryonic development.
Acquired: Some individuals are not born with mutations that cause hemophilia, but develop the disease later in life. This is referred to as acquired hemophilia. Acquired hemophilia is thought to occur when the immune system malfunctions and attacks clotting factor proteins, causing these proteins to malfunction. Acquired hemophilia is typically seen in older individuals, especially those over the age of 50.

Risk factors

General: Hemophilia B is usually inherited, or passed down, from parents. Because hemophilia can be inherited, the risk of disease increases in closely related families. In about 30% of cases, however, there is no family history of the disorder and the condition is the result of a spontaneous gene mutation.
Inheritance: Hemophilia is known to be caused by mutations, or errors, in specific genes that contain instructions for making clotting factors. These genes are located on the X chromosome, which is one of the sex chromosomes.
Females have two copies of the X chromosome, whereas males have one copy of the X chromosome and one copy of the Y chromosome. For a female to have hemophilia, both of her X chromosomes must carry a mutated clotting factor gene. If a female has only one abnormal clotting factor gene, she will not develop hemophilia because the normal gene on the other X chromosome can compensate for the defective gene. Males need to inherit only one mutated clotting factor gene to develop hemophilia because they do not have a second X chromosome that could provide a normal clotting factor gene. For this reason, males are affected by hemophilia much more often than females. If females have just one copy of the mutated gene, they are called carriers. Carriers of hemophilia generally do not experience any symptoms but may pass the mutated gene to their children.
A female who has a mutated clotting factor gene on one X chromosome has a 50% risk of passing the mutated gene to a son. If the mother has one mutated gene, therefore, each son will have a 50% chance of having hemophilia. A woman who has mutated clotting factor genes on both X chromosomes has a 100% chance of passing the mutation to a son. Each son of a mother with hemophilia will also have the disorder.
Because a male inherits an X chromosome from his mother, a male can inherit hemophilia only from his mother. Because a male passes a Y chromosome to his son, a male who has hemophilia cannot pass the mutation to his son(s). However, a male with hemophilia may pass the defective clotting factor gene to his daughter(s). Because males pass only X chromosomes to their daughters, each daughter of a male with hemophilia will carry one defective clotting factor gene.
Prevalence: Approximately 1 in 25,000 people worldwide are born with hemophilia B. Because hemophilia is an X-linked recessive condition, it occurs primarily in males. All races are affected equally.

Types of the disease

Severe: Patients with severe hemophilia B have less than 1% of normal factor IX activity. About 50% of people with hemophilia B have the severe form of the disease. These patients are at risk for spontaneous hemorrhages, often into the joints and muscles. Injuries may cause fatal bleeding to occur.
Moderate: People with moderate hemophilia B have 1 to 5% of normal factor IX activity. This type usually is diagnosed in children aged 1 to 2 years and accounts for 30% of all cases. These people may have occasional bleeding episodes without obvious causes.
Mild: Individuals with mild hemophilia B have greater than 5% of normal factor IX activity, and account for about 20% of all cases. These patients are at low risk for spontaneous bleeding but may bleed excessively following serious injury or surgery. In many cases, mild hemophilia is not discovered until an injury, surgery, or tooth extraction results in unusual bleeding. Mild hemophilia B may not be apparent or problematic until adulthood.