Haemophilia B

Haemophilia B

Hemophilia B is characterized by deficiency in factor IX clotting activity that results in prolonged oozing after injuries, tooth extractions, or surgery, and delayed or recurrent bleeding prior to complete wound healing. The age of diagnosis and frequency of bleeding episodes are related to the level of factor IX clotting activity. In severe hemophilia B, spontaneous joint or deep muscle bleeding is the most frequent symptom. Individuals with severe hemophilia B are usually diagnosed during the first year of life; without prophylactic treatment, they have an average of two to five spontaneous bleeding episodes each month. Individuals with moderately severe hemophilia B seldom have spontaneous bleeding; however, they 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. Individuals with mild hemophilia B do not have spontaneous bleeding; however, without preventive treatment, abnormal bleeding occurs with surgery, tooth extraction, and major injuries; the frequency of bleeding may vary from once a year to once every ten years. Individuals with mild hemophilia B are often not diagnosed until later in life. In any individual with hemophilia B, bleeding episodes may be more frequent in childhood and adolescence than in adulthood. Approximately 10% of carrier females are at risk for bleeding (even if the affected family member has mild hemophilia B) and are thus symptomatic carriers, although symptoms are usually mild.
Diagnosis/testing. The diagnosis of hemophilia B is established in individuals with low factor IX clotting activity. Molecular genetic testing of F9, the gene encoding factor IX, identifies disease-causing mutations in more than 99% of individuals with hemophilia B. Such testing is available clinically.
Management. Treatment of manifestations: referral to one of the approximately 140 federally funded hemophilia treatment centers (HTCs) for assessment, education, and genetic counseling; for those with severe disease, intravenous infusion of plasma-derived or recombinant factor IX concentrate within one hour of onset of bleeding. Training and home treatment with parental- followed by self-infusion are critical components of comprehensive care. Prevention of primary manifestations: For those with severe disease, prophylactic infusions of factor IX concentrate two to three times a week usually maintain factor IX clotting activity higher than 1% and prevent spontaneous bleeding. Prevention of secondary complications: reduction of chronic joint disease by prompt effective treatment of bleeding, including home therapy. Surveillance: For individuals with severe or moderately severe hemophilia B, annual assessments at an HTC are recommended; for individuals with mild hemophilia B, every two to three years; monitor carrier mothers for delayed bleeding post partum unless it is known that their baseline factor IX clotting activity is normal. Agents/circumstances to avoid: circumcision of at-risk males until hemophilia B is either excluded or treated with factor IX concentrate regardless of severity; intramuscular injections; activities with a high risk of trauma, particularly head injury; aspirin and all aspirin-containing products. Testing of relatives at risk: to clarify genetic status of females at risk before pregnancy or early in pregnancy, to facilitate management. Other: Vitamin K does not prevent or control bleeding in hemophilia B; no clinical trials for gene therapy in hemophilia B are currently in progress although several improved approaches are in pre-clinical testing.