Hemophilia - Factor VIII Carrier

Hemophilia - Factor VIII Carrier

 

Hemophilia A is an X-linked chromosomal disorder caused by defective synthesis of Factor VIII.

Epidemiology

  • Prevalence –  1-5/7,000 male births
  • Age
    • Severe disease – usually diagnosed in first year of life
    • Moderate disease – usually diagnosed before age 6
    • Mild disease – may not be diagnosed until adulthood

Inheritance

  • Inherited in an X-linked recessive manner
  • Female offspring of affected male parent are always carriers
  • F8 is the only known gene to cause Hemophilia A
    • Most common gene inversions – intron 22 and intron 1

Clinical Presentation

  • Excessive bleeding into various organs characterizes the disease
  • Severity based on Factor VIII levels
    • Most carriers have ≥50% factor activity
    • Mild – 6-30% of normal; no spontaneous bleeding
    • Moderate – 1-5% of normal; seldom have spontaneous bleeding
    • Severe – <1% of normal; spontaneous bleeding
  • Hemarthroses
    • Represents 75% of bleeding episodes
    • Repeated hemorrhage results in articular cartilage destruction
      • Target joints – most often knees, ankles, elbows
  • Hematomas
    • May be spontaneous
    • Muscle hemorrhage most common in calf, buttocks and forearm
  • Pseudotumors
    • Rare blood cysts that occur in soft tissue or bone
  • Hematuria
    • Common complication in severe hemophilia
  • Neurologic complications
    • Intracranial bleeding is the most dangerous event
    • Peripheral nerve root compression from muscle hematomas
  • Mucous membrane hemorrhage
  • Dental and surgical bleeding

Diagnosis

  • Laboratory testing
    • PTT is prolonged in moderate and severe hemophilia
    • PT, thrombin clotting time and bleeding time are normal
    • Factor VIII levels are abnormal
    • von Willebrand factor level is normal

Differential Diagnosis

  • von Willebrand disease
  • Factor deficiencies – XI, XII, prekallikrein, high molecular weight kininogen
  • Hemophilia B
  • Rare factor deficiencies – II, V, X, VII, fibrinogen
  • Platelet function disorders – Bernard-Soulier syndrome, Glanzmann thrombasthenia

Treatment

  • Factor replacement
  • Avoidance of non-steroidal anti-inflammatory drugs, antiplatelet drugs
  • Desmopressin
  • Antifibrinolytic agents

Prognosis

  • Much improved prognosis with the advent of factor replacement
  • Infectious complications of factor replacement therapy, mostly related to therapy prior to 1985, reduced lifespan secondary to hepatitis and HIV

See Also