What is the treatment for hemophilia?

Treatment of Hemophilia

First-line treatment for hemophilia includes recombinant activated factor VII (rFVIIa) and activated prothrombin complex concentrates (aPCCs) to achieve efficient hemostasis in patients with bleeding episodes. 1

Types of Hemophilia and Treatment Approach

• Hemophilia is a congenital X-linked bleeding disorder with hemophilia A (factor VIII deficiency) accounting for 80-85% of cases and hemophilia B (factor IX deficiency) accounting for the remainder 1
• Severity classification is based on factor levels:
  • Severe: <1 IU/dL
  • Moderate: 1-5 IU/dL
  • Mild: >5-40 IU/dL 1

First-Line Treatment Options

For Congenital Hemophilia A and B

• Factor replacement therapy:
  • Plasma-derived or recombinant factor concentrates (standard and extended half-life) 1
  • Prophylactic administration is preferred over on-demand treatment to prevent spontaneous bleeding and joint damage 2

For Acquired Hemophilia A (AHA)

• Bypassing agents are first-line treatments:
  • Recombinant activated factor VII (rFVIIa)
  • Activated prothrombin complex concentrates (aPCCs) 1
  • Response rates: rFVIIa is effective or partially effective in 90% of non-surgical cases and 86% of surgical cases 1

Dosing and Administration

For Hemophilia A and von Willebrand's Disease (Type I)

• Desmopressin (DDAVP):
  • Dosage: 0.3 mcg/kg actual body weight (maximum 20 mcg)
  • Administration: intravenous infusion over 15-30 minutes
  • Timing: 30 minutes prior to procedures if used preoperatively
  • Repeat dosing: may be repeated after 8-12 hours and once daily thereafter based on clinical condition and factor levels 3
  • Best reserved for minor bleeding episodes and patients with very low titer inhibitors 1

For Bypassing Agents in AHA

• rFVIIa regimens:
  • Bolus injection: 46-150 mcg/kg every 2-24 hours, or
  • Continuous infusion: 8-50 mcg/kg/hour 1
  • Treatment duration: typically 24-72 hours until bleeding is controlled 1

Inhibitor Management

• Inhibitor development is a major complication:

  • Cumulative incidence: 20-35% in severe hemophilia A and 4-9% in severe hemophilia B 1
  • For patients with inhibitors, bypassing agents are required 1

• For AHA with inhibitors:

  • All patients should receive immunosuppressive therapy immediately following diagnosis 1
  • Initial treatment: corticosteroids (1 mg/kg/day PO for 4-6 weeks) alone or in combination with cyclophosphamide (1.5-2 mg/kg/day for up to six weeks) 1
  • If no response after 4-6 weeks: consider rituximab alone or in combination with corticosteroids 1

Special Considerations and Precautions

• Monitoring requirements:

  • Prior to treatment: verify factor VIII coagulant activity levels are >5% and exclude inhibitors 3
  • During treatment: assess serum sodium, bleeding time, factor VIII coagulant activity 3

• Thromboembolic risk:

  • Higher risk in AHA patients (typically elderly) compared to congenital hemophilia 1
  • Use caution in patients with risk factors such as advanced atherosclerotic disease, crush injury, septicemia 1

• Prevention of iatrogenic bleeding:

  • Avoid invasive procedures when possible
  • Delay surgery until inhibitor eradication when feasible
  • Use prophylactic bypassing agents prior to invasive procedures 1

Emerging Therapies

• Extended half-life factor concentrates have improved quality of life by reducing frequency of infusions 4
• Gene therapy shows promise as a potential cure, though results from clinical trials have not yet achieved complete or long-lasting correction 5

Common Pitfalls to Avoid

• Do not rely on inhibitor levels to predict bleeding risk in AHA patients 1
• Avoid combination therapy with rFVIIa and aPCC except in life- or limb-threatening bleeds due to thrombotic risk 1
• Monitor for hyponatremia with desmopressin, particularly in elderly patients 1
• Do not use tranexamic acid with aPCC as it is contraindicated 1
• Do not delay immunosuppressive therapy in AHA patients as mortality without treatment is 41% compared to 20% with treatment 1