What type of hemophilia is caused by a factor 8 (FVIII) deficiency?

Factor VIII Deficiency is Hemophilia A

Factor VIII (FVIII) deficiency is definitively classified as Hemophilia A, which is an X-linked congenital bleeding disorder. 1

Classification and Severity

Hemophilia A is characterized by a deficiency of functional coagulation factor VIII (FVIII), which is encoded by the F8 gene and primarily produced by liver sinusoidal endothelial cells 2. The severity of Hemophilia A is classified based on factor VIII levels:

• Severe: FVIII levels <1 IU/dL
• Moderate: FVIII levels 1-5 IU/dL
• Mild: FVIII levels >5-40 IU/dL 1

Epidemiology and Genetics

• Hemophilia A is more common than Hemophilia B, accounting for approximately 80-85% of all hemophilia cases 2
• The estimated prevalence of Hemophilia A at birth is 24.6 cases per 100,000 males 1
• It is an X-linked recessive disorder, primarily affecting males, though females can be carriers and occasionally symptomatic 3
• The F8 gene is located on the X chromosome, and mutations in this gene cause Hemophilia A 2

Clinical Manifestations

Patients with Hemophilia A experience:

• Spontaneous and trauma-induced recurrent bleeding, especially in joints and muscles in severe cases 2
• Development of painful and disabling hemophilic arthropathy over time 2
• Potential life-threatening bleeding in the brain and other internal organs 2
• Varying clinical presentations based on severity, with mild cases typically bleeding only after surgery or trauma 2

Diagnostic Distinction from Other Bleeding Disorders

It's important to distinguish Hemophilia A (Factor VIII deficiency) from:

• Hemophilia B: Factor IX deficiency 2
• Von Willebrand Disease: Deficiency or dysfunction of von Willebrand factor, which carries and stabilizes Factor VIII in circulation 1, 4

Treatment Approaches

The standard of care for Hemophilia A includes:

• Prophylaxis with FVIII replacement products for severely affected patients, requiring regular IV infusions (at least once per week) 2
• Emicizumab, a subcutaneously administered FVIII-mimetic bispecific monoclonal antibody, approved for Hemophilia A prophylaxis 2
• Gene therapy using recombinant adeno-associated virus (AAV) vectors to transfer functional F8 genetic information into hepatocytes 2

Complications

A major complication in Hemophilia A treatment is the development of neutralizing antibodies (inhibitors) against infused FVIII:

• Occurs in 20-35% of patients with severe Hemophilia A 1
• Higher incidence compared to Hemophilia B (4-9%) 2
• Requires alternative treatment strategies such as bypassing agents (recombinant activated FVII or activated prothrombin complex concentrate) 1

Clinical Pearls

• Always confirm the specific type of hemophilia (A vs B) before initiating treatment, as the replacement factors differ
• Factor VIII levels correlate with bleeding risk and should guide prophylactic treatment decisions
• Genetic testing can identify specific F8 mutations, which may help predict inhibitor development risk 5
• Prophylactic therapy significantly improves quality of life compared to on-demand treatment 1

Remember that while both Hemophilia A and B present with similar bleeding symptoms, the specific factor deficiency (VIII vs IX) determines the diagnosis and treatment approach.