What are the treatment options for immune thrombocytopenia (ITP)?

Treatment Options for Immune Thrombocytopenia (ITP)

The treatment of immune thrombocytopenia (ITP) should follow a stepwise approach, with first-line therapies including corticosteroids, intravenous immunoglobulin (IVIg), and IV anti-D immunoglobulin, followed by second-line options such as thrombopoietin receptor agonists, rituximab, or splenectomy if initial treatments fail. 1

First-Line Treatment Options

Adults

1. Corticosteroids:

   • Standard: Prednisone 1-2 mg/kg/day 1
   • Alternative: High-dose dexamethasone (40 mg/day for 4 days) 1
   • Response rate: 60-80% initially, but many patients relapse 2
   • Caution: Should be used for short duration due to side effects 1

2. Intravenous Immunoglobulin (IVIg):

   • Dosing: 1 g/kg as a single dose or divided over 2 days 1
   • Rapid response within 24-48 hours 1
   • Response rate: >80% of patients 1
   • Use when rapid platelet increase needed 1
   • Limitations: Temporary effect, expensive, risk of headaches, thrombosis, renal failure 1

3. IV Anti-D Immunoglobulin:

   • For Rh(D)-positive, non-splenectomized patients only 1
   • Dosing: Short infusion 1
   • Side effects: Mild extravascular hemolysis common; rare cases of intravascular hemolysis, DIC, renal failure 1

Children

• Similar options as adults, but emphasis on short-course treatments 1
• IVIg (0.8-1 g/kg single dose) preferred in many cases 1
• Prednisone (1-2 mg/kg/day) or high-dose methylprednisolone for short duration 1
• Anti-D for Rh(D)-positive, non-splenectomized children 1

Emergency Treatment for Severe Bleeding

For life-threatening or organ-threatening bleeding:

• Combination therapy: IVIg + high-dose corticosteroids 1, 3
• Consider platelet transfusions (larger-than-usual dose) with IVIg 1
• Emergency splenectomy may be considered in special circumstances 1
• High-dose methylprednisolone may be useful 1

Second-Line Treatment Options

When first-line therapies fail to achieve durable response:

Thrombopoietin Receptor Agonists

• Eltrombopag:

  • FDA-approved for persistent/chronic ITP in adults and children ≥6 years 4
  • Initial dose: 36 mg once daily (18 mg for East/Southeast Asian patients or those with hepatic impairment) 4
  • Response rate: 50-60% 3
  • Use only in patients whose degree of thrombocytopenia increases bleeding risk 4

• Romiplostim:

  • FDA-approved for ITP in adults and children ≥1 year with insufficient response to other therapies 5
  • Should not be used to normalize platelet counts 5
  • Response rate: 50-60% 3

Rituximab

• Dosing: 375 mg/m² weekly for 4 weeks 1
• Response rate: 60% initially, with 40% achieving complete response 1
• Long-term responses in 20-30% of cases 3
• Side effects generally mild but can include serum sickness and rare severe reactions 1

Splenectomy

• Long-term response rate: 60-70% 1
• 80% of responders maintain response over 4 years 1
• Rapid response (within 24 hours) 1
• Major concern: Risk of post-splenectomy sepsis 1
• Generally deferred until other options exhausted due to permanent nature 2

Other Immunosuppressive Options

• Azathioprine: 1-2 mg/kg/day, response in up to two-thirds of patients 1
• Cyclosporin A: 5 mg/kg/day for 6 days then 2.5-3 mg/kg/day, 50-80% response rate 1
• Mycophenolate mofetil: 1000 mg twice daily, up to 75% response rate 1
• Dapsone: 75-100 mg daily, response in up to 50% of patients 1
• Danazol: 200 mg 2-4 times daily, 40-67% response rate 1

Treatment Algorithm

1. Initial Assessment:

   • Determine if treatment is needed based on bleeding symptoms and platelet count
   • Treatment generally indicated for:
     • Platelet count <20-30 × 10⁹/L regardless of symptoms 6
     • Platelet count <50 × 10⁹/L with significant bleeding 6

2. First-Line Treatment:

   • For non-emergency cases: Corticosteroids
   • For rapid response needed: IVIg or anti-D (if Rh-positive)
   • For life-threatening bleeding: Combination of IVIg + high-dose corticosteroids ± platelet transfusion

3. If No Response or Relapse After First-Line:

   • Consider thrombopoietin receptor agonists (eltrombopag or romiplostim)
   • Alternative: Rituximab
   • Splenectomy may be considered but often deferred due to permanent nature

4. For Chronic Refractory ITP:

   • Consider combination therapies
   • Trial of immunosuppressive agents
   • Continued use of thrombopoietin receptor agonists

Important Considerations

• Treatment Goal: Achieve safe platelet count to prevent bleeding, not normalize platelet count 1, 5
• Monitoring: Weekly platelet counts during dose adjustment, monthly once stable 3
• Pregnancy: Corticosteroids or IVIg preferred; delivery method based on obstetric indications 3
• Comorbidities: Check for HIV, hepatitis C, and H. pylori, as treating these may improve platelet counts 3
• Avoid: Medications that impair platelet function (e.g., NSAIDs, aspirin) unless absolutely necessary 1

Pitfalls to Avoid

1. Treating based on platelet count alone rather than bleeding symptoms
2. Prolonged corticosteroid use, especially in children
3. Using anti-D in Rh-negative or splenectomized patients
4. Attempting to normalize platelet counts with thrombopoietin receptor agonists
5. Delaying emergency treatment in cases of severe bleeding
6. Failing to consider and treat underlying conditions that may cause secondary ITP