What does a low factor VIII (8) activity level mean?

Low Factor VIII Activity: Diagnosis and Clinical Implications

A low factor VIII activity level indicates hemophilia A, with severity classified as severe (<1%), moderate (1-5%), or mild (>5% to <40% of normal). 1 This classification correlates well with clinical bleeding patterns in most patients and guides treatment decisions.

Classification of Factor VIII Deficiency

Factor VIII deficiency (hemophilia A) is categorized based on plasma activity levels:

• Severe hemophilia A: <1% of normal factor VIII activity

  • Associated with spontaneous bleeding, particularly into joints and muscles
  • Markedly prolonged aPTT

• Moderate hemophilia A: 1-5% of normal factor VIII activity

  • Occasional spontaneous bleeding and prolonged bleeding after minor trauma
  • Moderately prolonged aPTT

• Mild hemophilia A: >5% to <40% of normal factor VIII activity

  • Bleeding typically only after significant trauma or surgery
  • Mildly prolonged or normal aPTT 2

Causes of Low Factor VIII Activity

Low factor VIII activity can result from:

1. Congenital hemophilia A

   • X-linked recessive disorder primarily affecting males
   • Prevalence: approximately 1 in 5,000 males 1

2. Acquired hemophilia A

   • Due to autoantibodies against factor VIII
   • Associated with:
     • Postpartum period
     • Autoimmune disorders
     • Malignancies
     • Dermatologic disorders
     • Adverse drug reactions
     • Idiopathic cases 2

3. Von Willebrand Disease (VWD)

   • Can cause secondary reduction in factor VIII levels
   • Most common inherited bleeding disorder (prevalence 1/1000) 1

Clinical Manifestations

The clinical presentation correlates with the severity of factor VIII deficiency:

• Severe deficiency:

  • Spontaneous hemarthroses (joint bleeds)
  • Muscle hematomas
  • Intracranial hemorrhage (5-12% risk) 1
  • Bleeding after minor trauma

• Moderate deficiency:

  • Occasional spontaneous bleeding
  • Prolonged bleeding after injuries or surgery

• Mild deficiency:

  • Typically asymptomatic in daily life
  • Excessive bleeding after surgery or trauma

Diagnostic Considerations

When interpreting low factor VIII activity, consider:

1. Laboratory testing limitations:

   • Different aPTT reagents have varying sensitivities to factor deficiencies
   • Relying solely on aPTT may miss mild factor VIII deficiency 2
   • Discrepancies can occur between one-stage and chromogenic assays 3

2. Potential inhibitors:

   • Inhibitors are antibodies that neutralize factor VIII activity
   • Clinically significant inhibitor levels are ≥0.6 Bethesda Units/mL on two separate occasions 1
   • Inhibitor testing requires a washout period of at least 48 hours after factor infusion 1

3. Lupus anticoagulant interference:

   • Can cause falsely low factor VIII levels 2

Important Clinical Considerations

1. Bleeding risk assessment:

   • Factor level alone may not perfectly predict bleeding risk
   • Clinical history remains valuable in predicting bleeding tendency 4

2. Genetic implications:

   • X-linked inheritance pattern for congenital hemophilia A
   • Carrier testing important for female relatives 2

3. Treatment planning:

   • Factor replacement therapy based on severity and clinical situation
   • Inhibitor presence requires alternative treatment strategies 2

Common Pitfalls to Avoid

1. Missing mild hemophilia:

   • Relying solely on aPTT without specific factor assays may miss mild deficiency 2

2. Inadequate inhibitor testing:

   • Testing too soon after factor replacement can mask inhibitors
   • Multiple tests may be needed to confirm inhibitor status 1

3. Overlooking acquired hemophilia:

   • Consider in patients with new-onset bleeding without prior history
   • Particularly important in elderly patients or postpartum women 2

4. Misinterpreting factor levels between 40-50%:

   • Classification of individuals with FVIII levels between 40-50% remains unresolved 1

Low factor VIII activity is a significant finding that requires careful interpretation in clinical context, with appropriate follow-up testing and specialist consultation to ensure proper diagnosis and management.