Hemophilia

Basics

Description

  • Hemophilia A is factor VIII deficiency, and hemophilia B is factor IX deficiency.
  • Deficiency or absence of factor VIII or factor IX leads to a delay and disruption of blood clotting that results in prolonged bleeding.
  • The severity of bleeding depends on the baseline percentage of clotting activity that is genetically determined.

Epidemiology

  • Most common severe inherited bleeding disorder
  • Distribution
    • Hemophilia A: 80–85%
    • Hemophilia B: 10–15%
  • No geographic or ethnic associations

Incidence

  • Hemophilia A: 1 per 5,000 male births
  • Hemophilia B: 1 per 30,000 male births

Risk Factors

Genetics

  • X-linked recessive disorder
  • Daughters of fathers with hemophilia are obligate carriers for the hemophilia gene mutation. An obligate carrier has a 50% chance of passing the hemophilia gene mutations to her offspring.
  • Carrier status and prenatal testing available
  • Hemophilia A
    • The intron 22 inversion mutation in the factor VIII gene is found in ~40–50% of patients with severe hemophilia A.
  • Hemophilia B
    • Most factor IX gene defects are single base pair changes that result in missense, frameshift, or nonsense mutations. Mutations have been detected in all regions of the factor IX gene.

General Prevention

  • Prophylaxis: the regularly scheduled infusion of clotting factor concentrate with the goal of preventing bleeding episodes; primarily used in patients with severe disease
  • Anticipatory guidance and prevention
    • Good dental hygiene
    • Immunizations: no intramuscular injections; give subcutaneously with a small-gauge needle and apply direct pressure.
    • Rapid treatment of hemarthrosis to avoid chronic joint damage
    • Avoidance of contact sports (e.g., football, hockey, rugby)
    • Encourage physical fitness to ensure strong muscles to maintain joint health and prevent joint bleeding.
    • Head trauma precautions

Pathophysiology

  • Both factors VIII and IX are crucial for normal thrombin generation via the intrinsic pathway. The absence or decrease in activity of either protein severely impairs the ability to generate thrombin and fibrin.
  • Hemophilia patients do not bleed more rapidly; rather, there is delayed formation of an abnormal clot resulting in prolonged bleeding.

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