What is it?
Hemophilia is a bleeding disorder caused by a deficiency in one of the blood clotting factors. Hemophilia B (also called “Christmas disease” after Stephen Christmas, a 20th-century British boy who was first diagnosed with it) is a deficiency in clotting factor IX.
Hemophilia A is 7 times more common than hemophilia B. The incidence of hemophilia B is 1 out of 34,500 men.
Hemophilia B is a hereditary disorder in which the clotting ability of the blood is impaired and prolonged bleeding results. Small wounds and punctures are usually not a problem. But uncontrolled internal bleeding can result in pain and swelling and permanent damage, especially to joints and muscles.
The outcome is good with treatment and management. Most people with Hemophilia B are able to lead relatively normal lives.
Hemophilia B is caused by an inherited sex-linked recessive trait with the defective gene located on the X chromosome. Females are carriers of this trait. Fifty percent of the male offspring of female carriers will have the disease, and 50% of their female offspring will be carriers. All female children of a male with hemophilia will be carriers of the trait.
One fifth of all cases of hemophilia B occur when there is no family history of the disorder. In these cases, hemophilia develops as the result of a new or spontaneous gene mutation.
Genetic counseling may be advised for carriers. Female carriers can be identified by testing.
A woman is definitely a hemophilia carrier if she is:
- The biological daughter of a man with hemophilia
- The biological mother of more than one son with hemophilia
- The biological mother of one hemophilic son and has at least one other blood relative with hemophilia
A woman may or may not be a hemophilia carrier if she is:
- The biological mother of one son with hemophilia
- The sister of a male with hemophilia
- An aunt, cousin, or niece of an affected male related through maternal ties
- The biological grandmother of one grandson with hemophilia
Symptoms & Diagnosis
Hemophilia is caused by several different gene abnormalities. Severity of Hemophilia B symptoms depends on how a particular gene abnormality affects the activity of factor IX. When the activity is less than 1 percent of normal, episodes of prolonged bleeding may occur for no apparent reason.
Severity of symptoms can vary, but severe forms become apparent early on. Prolonged bleeding is the disease’s hallmark and typically manifests itself when an infant is circumcised. Additional bleeding manifestations make their appearance when the infant becomes mobile. Mild cases may go unnoticed until later in life, when they occur in response to surgery or trauma. Internal bleeding may occur anywhere and bleeding into joints is common.
Risk factors are a family history of bleeding and being male. The incidence of hemophilia B is 1 out of 34,500 men.
- Spontaneous bleeding
- Bleeding into joints and associated pain and swelling
- Gastrointestinal tract and urinary tract hemorrhage
- Blood in the urine or stool
- Prolonged bleeding from cuts, tooth extraction, and surgery
- Prolonged bleeding following circumcision
People whose clotting activity is 5 percent of normal may have only mild hemophilia. They rarely have unprovoked bleeding episodes, but surgery or injury may cause uncontrolled bleeding, which can be fatal. Milder hemophilia may not be diagnosed at all, although some people whose clotting activity is 10 to 25 percent of normal may bleed excessively after surgery, dental extractions, or a major injury.
Generally, the first bleeding episode occurs before 18 months of age, often after a minor injury. A child who has hemophilia bruises easily. Even an injection into a muscle can cause bleeding that results in a large bruise (hematoma). Continuous bleeding into the joints and muscles can ultimately lead to crippling deformities. Bleeding can swell the base of the tongue until it blocks the airway, making breathing difficult. A slight bump on the head can trigger substantial bleeding in the skull, causing brain damage and death.
A doctor may suspect hemophilia in a child whose bleeding is unusual. A laboratory analysis of blood samples can determine whether the child’s clotting is abnormally slow. If it is, the doctor can confirm the diagnosis of hemophilia and can determine the severity by testing the activity of factor IX.
Coagulation studies involving many tests are performed if the person tested is the first one in the family to have the bleeding disorder. Once the defect has been identified, other family members will need less testing to diagnose the disorder.
Like hemophilia A, hemophilia B is typically treated by infusing the missing clotting factor. The amount infused depends upon the severity of bleeding, the site of the bleeding, and the size of the patient. 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.
Clotting factors are found in plasma and, to a greater extent, in plasma concentrates. Some plasma concentrates are intended for home use and can be self-administered, either on a regular basis to prevent bleeding or at the first sign of bleeding. More often, they are administered three times a week (prophylaxis), but both the dose and frequency depend on the severity of the bleeding problem. The dose is adjusted according to the results of periodic blood tests. During a bleeding episode, more clotting factors are needed. Treatment should be coordinated by a health care practitioner who is expert in the disease.
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 regular prophylaxis infusions two to three time a week. Depending on the severity of the disease, factor IX concentrate may be given prior to dental extractions and surgery to prevent bleeding.
Gene therapy and fetal tissue implant techniques are under study as possible treatments.
People who have hemophilia should avoid situations that might provoke bleeding. They should be conscientious about dental care so they won’t need to have teeth extracted. If people who have milder forms of hemophilia need to have dental or other surgery, the drug desmopressin acetate (DDAVP may be given to improve clotting temporarily so that transfusions can be avoided.
People who have hemophilia should also avoid certain drugs that can aggravate bleeding problems:
- Certain analgesics such as nonsteroidal anti-inflammatory drugs
The National Hemophilia Foundation’s Medical and Scientific Advisory Council (MASAC) made recommendations for treatment of hemophilia B in November of 1999. They include:
- Recombinant factor IX products for patients who are HIV seronegative, especially for young and newly diagnosed patients who have not received any blood or plasma-derived products.
- Today, plasma-derived factor IX products offer greatly reduced risk for HIV and hepatitis B and C transmission, but there is still some risk. Dry heating, solvent-detergent treatment, vapor treatment, and sodium thiocyanate plus ultrafiltration and are all effective purification steps but there remains a slight possibility of viral transmission.
- Patients who are HIV seropositive should also be treated with high purity products such as immunoaffinity purified and recombinant factor VIII products.
- For patients with inhibitors to factors VIII and IX, there is Recombinant Factor VIIa (NovoSeven). Produced by baby hamster kidney cells, no human albumin or other proteins are used in its production, reducing virus risk. There is also Porcine factor VIII (Hyate C), and activated prothrombin complex concentrates.
- Chronic joint deformities, caused by recurrent bleeding into the joint, may be managed by an orthopedic specialist.
- Intracerebral hemorrhage may also occur.
- Thrombosis may occur following use of factor IX concentrate.
Some persons with hemophilia develop antibodies to transfused factor IX. As a result, transfusions become ineffective. If antibodies are detected in blood samples, the dosage of the plasma concentrates may be increased, or different types of clotting factors or drugs to reduce the antibody levels may be used.
In the past, the plasma concentrates carried the risk of transmitting blood-borne diseases such as hepatitis and AIDS. About 60 percent of persons with hemophilia who were treated with plasma concentrates in the early 1980s were infected with HIV. However, the risk of transmitting HIV infection through plasma concentrates has been virtually eliminated by today’s use of screened and processed blood.