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For further information, see CMDT Part 14-08: Congenital Disorders of Coagulation

Key Features

Essentials of Diagnosis

  • Hemophilia A: congenital deficiency of coagulation factor VIII

  • Hemophilia B: congenital deficiency of coagulation factor IX

  • Recurrent hemarthroses and arthropathy

  • Risk of development of inhibitory antibodies to factor VII or factor IX

  • Many older patients received blood products contaminated with HIV or hepatitis C virus (HCV)

General Considerations

  • Inheritance is X-linked recessive, leading to affected males and carrier (affected) females with variable bleeding tendencies

  • Daughters of all affected males are obligate carriers

  • There is no race predilection

  • Inhibitors to factor VIII will develop in ~20–25% of patients with severe hemophilia A

  • Inhibitors to factor IX will develop in < 5% of patients with severe hemophilia B

  • Hemophilia is classified according to the level of factor activity in the plasma

    • Mild hemophilia is characterized by > 5% factor activity

    • Moderate hemophilia is characterized by 1–5% factor activity

    • Severe hemophilia is characterized by < 1% factor activity

Demographics

  • The frequency of hemophilia A is ~1 per 5000 live male births

  • Hemophilia B occurs in ~1 in 25,000 live male births

Clinical Findings

Symptoms and Signs

  • Severe hemophilia presents in infant males or in early childhood with spontaneous bleeding into joints, soft tissues, or other locations

  • Spontaneous bleeding is not common in patients with mild hemophilia, but significant bleeding is common during a major hemostatic challenge (eg, surgery, trauma)

  • Intermediate clinical symptoms are seen in patients with moderate hemophilia

  • Female carriers are can have a wide range of factor VIII activity, and therefore have variable bleeding tendencies

  • Joint disease

    • Significant hemophilic arthropathy

      • Usually does not develop in patients who have received long-term prophylaxis with factor concentrate in early childhood

      • Is common in adults who have experienced recurrent hemarthroses

    • Patients tend to have one or two 'target' joints into which they bleed most often

  • Development of inhibitor to factor VIII or factor IX is characterized by bleeding episodes that are resistant to treatment with clotting factor VIII or IX concentrate, and by new or atypical bleeding

Differential Diagnosis

  • Hemophilia B

  • von Willebrand disease

  • Disseminated intravascular coagulation

  • Heparin administration

  • Acquired factor deficiency or inhibitors (eg, paraproteins with anti-VIII or anti-IX activity)

Diagnosis

Laboratory Tests

  • Factor activity testing is indicated for

    • Male infants with a hemophilic maternal pedigree who are asymptomatic or who experience excessive bleeding

    • All daughters of affected males (100% chance of being affected) and carrier mothers (50% chance of being affected)

    • An otherwise asymptomatic adolescent or adult who experiences unexpected excessive bleeding with trauma or invasive procedures

  • An isolated reproducibly low factor VIII or factor IX activity level, in the absence of ...

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