What is the primary treatment for Haemophilia A (factor VIII deficiency)?

Primary Treatment for Hemophilia A

The primary treatment for Hemophilia A (factor VIII deficiency) is factor VIII replacement therapy, with prophylactic administration being the standard of care for patients with severe disease to prevent bleeding episodes and joint damage. 1

Classification and Assessment

• Hemophilia A severity is classified based on factor VIII activity levels:

  • Severe: <1% of normal
  • Moderate: 1-5% of normal
  • Mild: >5% to <40% of normal 1

• Diagnosis is confirmed through:

  • Prolonged activated partial thromboplastin time (aPTT)
  • Decreased factor VIII activity levels
  • Normal prothrombin time and platelet count
  • Bethesda assay to quantify inhibitors if present 1

Treatment Approaches

Factor VIII Replacement Therapy

• Dosing Guidelines:

  • Initial bolus: 20-50 IU/kg
  • Maintenance: 20-50 IU/kg every 6-8 hours or continuous infusion (3-4 IU/kg/h) 1
  • Dosing depends on:
    • Severity of bleeding
    • Patient's baseline factor VIII level
    • Target factor VIII level needed for hemostasis

• Treatment Regimens:

  • On-demand therapy: Factor VIII administered when bleeding occurs
  • Prophylaxis: Regular factor VIII infusions to prevent bleeding episodes (preferred for severe hemophilia A) 2

• Extended Half-Life Products:

  • Newer factor VIII products with extended half-life reduce infusion frequency
  • Technologies include Fc-fusion and PEGylation
  • Improve adherence and quality of life by reducing treatment burden 2

Special Situations

Mild Hemophilia A (Factor VIII >5%)

• Desmopressin (DDAVP) may be used for:
  • Patients with factor VIII levels >5%
  • Surgical procedures (administered 30 minutes prior)
  • Spontaneous or trauma-induced bleeding episodes 3
  • Not indicated for patients with factor VIII levels ≤5% 3

Patients with Inhibitors (15-30% of patients)

• Bypassing agents are the mainstay of treatment:

  • Recombinant activated factor VII (rFVIIa): 90 μg/kg every 2-3 hours until hemostasis
  • Activated prothrombin complex concentrates (aPCCs): 50-100 IU/kg every 8-12 hours (maximum 200 IU/kg/day) 1

• Emicizumab (FVIII-mimetic bispecific antibody):

  • Approved for prophylaxis in patients with/without inhibitors
  • Administered subcutaneously every 1-2 weeks
  • Factor VIII replacement still required for breakthrough bleeding 4

• Immune tolerance induction (ITI) for inhibitor eradication:

  • Corticosteroids (1 mg/kg/day for 4-6 weeks)
  • May be combined with cyclophosphamide (1.5-2 mg/kg/day for up to six weeks) 1

Emerging Therapies

• Gene therapy:
  • Shows promise for providing long-term endogenous FVIII production
  • Valoctocogene roxaparvovec is an AAV vector-based gene therapy that transfers functional F8 genetic information into hepatocytes 4
  • May potentially transform severe hemophilia to milder phenotype or essentially cure patients 5
  • Requires careful liver health assessment before and monitoring after treatment 4

Treatment Monitoring and Follow-up

• Regular monitoring of:

  • Factor VIII levels
  • Bleeding frequency and severity
  • Joint health
  • Inhibitor development (Bethesda assay) 1

• For invasive procedures:

  • Consult hematologist before scheduling
  • Administer factor replacement to achieve 50-100% factor activity
  • Continue replacement for appropriate duration based on procedure type 1

Pitfalls and Caveats

• Inhibitor development is the most significant treatment complication
• Delayed treatment initiation can lead to irreversible joint damage
• Inadequate dosing or duration of therapy may result in treatment failure
• Not switching treatment strategies when response is inadequate
• Using NSAIDs for pain management (contraindicated due to bleeding risk) 1

The treatment approach should be guided by the severity of hemophilia, presence of inhibitors, and individual bleeding patterns, with the goal of preventing bleeding episodes and preserving joint function to improve quality of life.