Hemophilia B

In: GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993.
[updated ].


Clinical characteristics: 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 any individual with hemophilia B, bleeding episodes may be more frequent in childhood and adolescence than in adulthood.

  1. Individuals with severe hemophilia B are usually diagnosed during the first two years of life. Without prophylactic treatment, they 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.

  2. Individuals with moderate hemophilia B seldom have spontaneous bleeding, although it varies between individuals; 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.

  3. Individuals with mild hemophilia B 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 hemophilia B are often not diagnosed until later in life.

Approximately 30% of heterozygous females have factor IX clotting activity lower than 40% and are at risk for bleeding (even if the affected family member has mild hemophilia B), although symptoms are usually mild. After major trauma or invasive procedures, prolonged or excessive bleeding usually occurs, regardless of severity.

Diagnosis/testing: The diagnosis of hemophilia B is established in individuals with low factor IX clotting activity. Identification of a hemizygous F9 pathogenic variant on molecular genetic testing in a male proband confirms the diagnosis. Identification of a heterozygous F9 pathogenic variant on molecular genetic testing in a symptomatic female confirms the diagnosis.

Management: Treatment of manifestations: Referral to a hemophilia treatment center (HTC) for assessment, education, genetic counseling, and treatment.

Targeted therapy: For those with severe disease, prophylactic infusions of factor IX concentrate 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. Some individuals with moderate hemophilia bleed frequently enough to benefit from prophylaxis. Longer-acting products that allow weekly or biweekly dosing are now available. Intravenous infusion of plasma-derived or recombinant factor IX for acute bleeding episodes should be given as soon as possible after symptoms occur. Training in home infusion should be provided for individuals/families affected by moderate and severe hemophilia.

Supportive care: Physical therapy for evaluation and treatment of musculoskeletal disease; standard treatments for pain with help from a pain specialist as needed; standard treatments for transfusion-related infections contracted prior to virucidal treatment of plasma-derived concentrates.

Surveillance: For young children with severe or moderate hemophilia B, assessments every six to 12 months at an HTC; older children and adults with severe or moderate hemophilia B benefit from at least annual assessment at an HTC; for individuals with mild hemophilia B, assessment at an HTC every one to two years. Individuals with comorbidities may require more frequent visits. The assessment should include a review of bleeding episodes, adjustment of treatment plans as needed, a joint and muscle evaluation, an inhibitor screen, viral testing if indicated, and a discussion of any other issues related to the individual's hemophilia B as well as family and community support. Screening for alloimmune inhibitors is performed after treatment with factor IX concentrates has been initiated and in any individual with a suboptimal clinical response to treatment.

Agents/circumstances to avoid: Circumcision of at-risk males until hemophilia B is either excluded or treated with factor IX concentrate regardless of severity; activities with a high risk of trauma, particularly head injury; aspirin and all aspirin-containing products. Cautious use of other medications and herbal remedies that affect platelet function. Use precaution with intramuscular injections (apply pressure and ice; intramuscular injection may be scheduled after factor IX treatment or while on prophylaxis).

Evaluation of relatives at risk: It is appropriate to evaluate asymptomatic male and female at-risk relatives of an affected individual in order to identify as early as possible those who would benefit from prompt initiation of targeted therapy, supportive care, and surveillance. It is recommended that the genetic status of at-risk females be established prior to pregnancy or as early in a pregnancy as possible.

Pregnancy management: Maternal factor IX levels do not increase during pregnancy and heterozygous females may need factor IX infusion support for delivery and/or to treat or prevent postpartum hemorrhage. Heterozygous mothers should be monitored for delayed bleeding postpartum. Tranexamic acid can be used to prevent postpartum hemorrhage.

Other: Vitamin K does not prevent or control bleeding in hemophilia B.

Genetic counseling: Hemophilia B is inherited in an X-linked manner. The risk to sibs of a male proband depends on the genetic status of the mother. The risk to sibs of a female proband depends on the genetic status of the mother and father. If the mother of the proband has an F9 pathogenic variant, the chance of the mother transmitting it in each pregnancy is 50%. If the father of the proband has an F9 pathogenic variant, he will transmit it to all his daughters and none of his sons. Males who inherit the pathogenic variant will be affected; females who inherit the pathogenic variant are heterozygotes and may be at risk for bleeding. Once the F9 pathogenic variant has been identified in an affected family member, genetic testing for at-risk family members, prenatal testing for a pregnancy at increased risk, and preimplantation genetic testing are possible.

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