Hemophilia B

The acuity and age of presentation of symptoms is dependent on the extent of the factor IX deficiency, as described above. Clotting factor deficiencies result in hematomas and hemarthroses. Hemarthroses is a hallmark presentation of hemophilia B [3]. It occurs when bleeding begins in the synovial vessels and hemorrhage occurs within the joint cavity. The bleeding results in distension of the synovial space and causes muscle spasms, pain and arthropathy. In infants, the disorder presents as irritability and decreased use of the affected limb. In older children and adults, hemarthrosis presents as stiffness and in some patients as a warm sensation followed by acute pain and swelling [4].

In neonates and infants, symptoms may include bleeding and hematoma following delivery, after procedures (such as circumcision) or spontaneously (such as an intracranial hemorrhage) [5]. As children begin to walk, bleeding episodes involve the joints and muscles. The onset of bleeding may be spontaneously or after minimal injury. Other common symptoms include excessive bruising, oral bleeding, epistaxis, hematuria, rectal bleeding, weakness, abdominal pain and tenderness, dyspnea and headache [6].

Diagnosis for hemophilia B is made through a family history, laboratory screening tests and specific assays. Approximately 70% of people with hemophilia B have a family history of the disease. However approximately one-third of patients do not have a family history of hemophilia B. In these patients, the disease may be a result of a spontaneous mutation [7].

Screening tests such as coagulation tests (prothrombin time (PT), activated partial thromboplastin time (aPTT) and a platelet count) can be used to help determine the etiology of the person’s symptoms. Persons with hemophilia A and B have a normal platelet count and normal PT, but have a prolonged aPTT. For those persons with a prolonged aPTT, assays for the various clotting factors (factors VIII, IX and XI) should be performed to identify the type of hemophilia. An abnormal assay for factor IX is diagnostic for hemophilia B.

The goal of treatment is to prevent bleeding and hemorrhage prophylactically, especially in patients with moderate to severe disease. Also to recognize and control bleeding when it occurs. Medications used in the treatment of hemophilia B include:

• Laboratory made factor IX (Recombinant factor IX) is often used for prophylactic treatment. Studies have shown that when recombinant coagulation factor IX is started during the early years of life on a routine basis as a prophylaxis treatment, there is a reduced the risk of hemorrhage and arthropathy [8]. The Medical and Scientific Advisory Council of the National Hemophilia Foundation supports prophylaxis therapy for children with severe hemophilia B [9] [10].
• Antifibrinolytics (epsilon aminocaproic acid, tranexamic acid)
• Antihemophilic agents (desmopressin acetate (a non-blood product), human antihemophilic factor)

Uncontrolled hemorrhage may lead to significant morbidity and/or death. Late complications of the disorder may include:

• Joint destruction due to hemarthroses, resulting in several orthopedic abnormalities
• Transmission of blood-borne infections (if factor IX is given through plasma transfusion)
• Development of inhibitor antibodies

In hemophilia B the protein (factor IX) needed to form blood clots is absent or reduced.

Hemophilia B affects 20% of all persons with hemophilia; it is the second most common type of hemophilia [1]. Its overall incidence is approximately 1 in 25,000 male births. The disorder is more symptomatic in males over females since it is an X-linked disorder. Females have two X-chromosomes. Therefore a recessive X-linked disorder will usually be “silenced” by the normal factor IX gene on the other X chromosome, thus preventing the expression of the disease. The woman is referred to as a “carrier”. Males have only one X chromosome, therefore any genetic mutations on the X chromosome, whether recessive or dominant, will be expressed. Its incidence is similar in all races and geographic areas.

When a blood vessel is injured, a series of biochemical reactions initiate the coagulation cascade. Various reactions involving protein factors such as factor IX, bind and activate other factors to form a clot on the injured blood vessel [2]. A majority of patients are diagnosed with hemophilia B prior to any bleeding event based on family history. Hemophilia B is an X-linked recessive disorder in which there is factor IX deficiency.

Levels of factor IX range from 70 to 120% of the normal values. There are different levels of hemophilia B depending on the degree of factor IX deficiency in the person’s blood. Persons with:

• Mild disease have at least or more than 5% factor level IX in their blood. Persons with mild disease may be essentially asymptomatic.
• Moderate disease have 1 to 5 % of the normal clotting factor IX. These patients tend to bleed after injuries and some bleed spontaneously. Symptoms generally onset in the mid-teens through middle age in patients with moderate disease.
• Severe hemophilia cases have less than 1% of the normal clotting factor IX in their blood. These patients have significant bleeding after injuries, frequent spontaneous bleeding episodes, and hemarthroses. Symptoms may appear as early during infancy in persons with severe factor IX deficiency.

There are no guidelines for prevention of hemophilia B.

Hemophilias are a group of inherited bleeding disorders characterized by deficiency of functional plasma coagulation factors. The different types of hemophilia include type A and type B. In this section we focus on the second most common type of hemophilia, hemophilia B, also called factor IX deficiency or Christmas disease. It was named “Christmas disease” after Stephen Christmas, who was the first patient diagnosed with the disorder in 1952. Hemophilia B is a disorder in which the protein (factor IX) needed to form blood clots is absent or reduced. It is an X-linked, recessive genetic disorder that is characterized by the deficiency of functional plasma protein coagulation factor IX, which results in prolonged bleeding and/or hemorrhage.

What is hemophilia B?

Hemophilia is a rare genetic blood clotting disorder that mainly affects men. People who have hemophilia do not have enough of, or are missing, one of the proteins required for clotting of blood called factor IX. There are different types of hemophilia: A, B and Von Willebrand disease. Hemophilia B is the second most common type of hemophilia. It is also known as Factor IX deficiency or “Christmas disease”. It was named “Christmas disease” after Stephen Christmas, who was the first patient diagnosed in 1952.

When a blood vessel is injured, the body starts a process that activates a series of proteins to form a clot to stop bleeding. A person with hemophilia B lacks one of the proteins required for this process, called factor IX. Therefore, a person with hemophilia B will bleed for a long time when they are injured or cut. Sometimes bleeding occurs spontaneously (without any apparent reason).

The severity of the disease depends on the amount of factor IX that is produced in the body. Hemophilia B is rated as:

• Mild: A person’s body makes at least or more than 5% of the factor level IX. The persons have milder disease or may not have any symptoms at all until later in life.
• Moderate: A person has 1 to 5% of the normal clotting factor IX. These persons bleed for a long time after injuries and also may develop spontaneous bleeding. Symptoms may begin during the teenage years through middle age.
• Severe: A person with less than 1% of the normal clotting factor IX in their blood is considered to have severe hemaphilia. These persons have significant bleeding after injuries, frequent spontaneous bleeding episodes, and hemarthroses (bleeding into their joints). Symptoms may appear as early during infancy.

What causes hemophilia B?

In most people, hemophilia B is inherited. It is caused by a recessive defect on a gene that is on the sex chromosome “X”. Women have two X chromosomes, therefore if a woman has one defective gene on one X chromosome, but a normal gene for factor IX on her other X chromosome, she will usually not show any symptoms. She is a carrier and may pass the gene onto her children. Men have only one X chromosome. Therefore a defective gene on their X chromosome will result in their having symptoms of the disorder. Therefore, hemophilia B symptoms are more common in men than women. In some people, a “spontaneous mutation” occurs in their gene that causes them to develop hemophilia B.

What are the symptoms of hemophilia B?

Symptoms are usually prolonged bleeding and hematoma (a large bruise). In babies this may happen after or during delivery or after procedures (such as circumcision). Sometimes the bleeding occurs without any apparent reason (such as bleeding in the brain). As children begin to walk, bleeding may occur in joints and muscles. Other symptoms include excessive bruising or blood in the urine.

How is it diagnosed?

Diagnosis for hemophilia B is made through a family history screening, laboratory blood tests and specific assays. Your doctor will ask you about your family’s medical history. In particular if any member of your family has a bleeding disorder. Approximately 70% of people with hemophilia B have a relative with a bleeding disorder. However approximately one-third of patients do not have a family history of hemophilia B. In these patients, the disease may be a result of a spontaneous mutation.

If your doctor suspects a bleeding disorder, he/she will order laboratory tests to determine if a bleeding disorder is present and the type of disorder. Laboratory blood tests, called a coagulation panel, include prothrombin time (PT), activated partial thromboplastin time (aPTT) and a platelet count. Persons with hemophilia A and B have a normal platelet count and normal PT, but have a prolonged aPTT. For those persons with a prolonged aPTT, assays to determine the levels of the various clotting factors (Factors VIII, IX and XI) will be performed to identify the type of hemophilia. This is also a blood test. An abnormal assay for Factor IX is diagnostic for hemophilia B.

What is the treatment?

Currently there is no cure for hemophilia. However there are laboratory made factor IX replacements that can be given as prophylaxis. This means that the medication can help prevent symptoms such as bleeding and hemorrhaging. One commonly used medication is called “recombinant factor IX”. This medication is given intravenously (by IV). It is made in the laboratory and mimics the factor IX that a healthy person’s body makes. It is often given on a routine basis as a prophylactic (preventative) treatment. There are additional medications available and your doctor can discuss those options with you.

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