1. Background

• Factor VIII is a complex of two components each with different genetic control and biochemical functions:
  1. Factor VIIIc - coagulation protein
  2. Factor VIIIvW - platelet adhesion protein
• Factor VIIIc is the final component of the Intrinsic Pathway and in the presence of activated Factor IX, activates Factor
• X within the Common Pathway
• Factor VIIIc is complexed with Factor VIIIvW, the latter acting as a carrier protein
• in Hemophilia A, the plasma levels of Factor VIIIvW are normal
  • female carriers and male fetuses in utero have a Factor VIIIc/Factor VIIIvW ratio less than 1 (normally this ratio is equal to 1)

2. Genetic Defect

• genetic defect -> deficiency of Factor VIIIc -> clinical severity related to the level of Factor VIIIc:
  1. Severe

  • Factor VIIIc activity is < 1% of normal
  • onset of bleeding in the newborn period
    • Factor VIIIc does not cross the placenta
    • hematomas after injections or circumcision
    • hemarthroses and deep tissue hemorrhages
  • bleeding may be spontaneous
  • clinical evidence of increased bleeding in 90% of these patients by 1 yr of age
  2. Moderate

  • Factor VIIIc activity is 1-5% of normal
  • onset of bleeding during infancy
    • excessive bruising with ambulation
    • some arthrosis
  • bleeding may be spontaneous but usually following mild to moderate trauma
  3. Mild

  • Factor VIIIc activity is > 6% of normal
  • onset of bleeding during childhood
  • bleeding is not spontaneous and follows moderate to severe trauma, dental work, or surgery

1. Common Sites of Hemorrhage

1. Serum

• prolonged PTT
• decreased Factor VIIIc
• normal PT, bleeding time, thrombin time, platelet count, Factor
• VIIIvW

1. Supportive

• avoid trauma and anticoagulants (i.e., ASA)
• pad crib and playpen
• pressure and cold compresses to bleeding sites
• initially immobilize affected area then passive exercises within 48 hrs to prevent stiffness and fibrosis
• immunize against hepatitis B

2. Replacement Therapy