What is the primary treatment approach for a patient with Immune Thrombocytopenic Purpura (ITP)?

Primary Treatment Approach for Immune Thrombocytopenic Purpura (ITP)

The primary treatment goal for ITP is achieving a hemostatic platelet count (≥30-50 × 10⁹/L) to prevent major bleeding, not normalizing platelet counts, and treatment should only be initiated when thrombocytopenia severity and clinical condition increase bleeding risk—not based on platelet numbers alone. 1, 2

When to Treat vs. Observe

• No treatment is required if platelet count >50 × 10⁹/L unless active bleeding, planned surgery, bleeding-predisposing comorbidities, or need for anticoagulation exists 2
• Treatment is indicated for platelet counts <30 × 10⁹/L with bleeding symptoms, or <20 × 10⁹/L regardless of symptoms 2
• The severity of bleeding does not always correlate with platelet count; age, lifestyle, and comorbidities affect bleeding risk 2

First-Line Treatment Strategy

Standard Corticosteroid Therapy

High-dose dexamethasone 40 mg daily for 4 days is superior to conventional prednisone, offering initial response rates of 86-90% with sustained responses in 50-80% of patients 1, 2. This can be given as a single cycle or up to 4 cycles every 14 days 1.

Alternative: Prednisone 0.5-2 mg/kg/day until platelet count increases to 30-50 × 10⁹/L, which may require several days to several weeks 1. Prednisone should be rapidly tapered and stopped in responders, and especially in non-responders after 4 weeks to avoid corticosteroid-related complications 1.

Adjunctive Therapy for Rapid Response

IVIg 1 g/kg as a single dose can be combined with corticosteroids when faster platelet response is required 2.

Critical Corticosteroid Pitfall

Avoid prolonged corticosteroid use beyond 6-8 weeks due to risks of weight gain, osteoporosis, cataracts, infections, and paradoxically increased bleeding risk 3. Detrimental effects often outweigh benefits with extended therapy 1.

Emergency Treatment for Active Bleeding

For uncontrolled bleeding or active CNS, GI, or genitourinary bleeding, combine prednisone and IVIg 1. High-dose methylprednisolone may also be useful in emergency settings 1.

Platelet transfusion at larger-than-usual doses, possibly in combination with IVIg, should be considered in life-threatening situations 1.

Second-Line Treatment Hierarchy

First Choice: Thrombopoietin Receptor Agonists (TPO-RAs)

TPO-RAs (romiplostim and eltrombopag) should be the initial second-line therapy for refractory ITP, with overall platelet response rates of 88% in non-splenectomized patients and 79% in splenectomized patients 3. These are the only therapies specifically developed to treat ITP 3.

Key advantages of TPO-RAs:

• Sustained responses documented for up to 4 years with continuous administration 3
• Up to 30% of patients achieve long-term remission after tapering and discontinuation 3
• Well-tolerated for long-term management with favorable safety profiles 3
• No increased risk of infections, thromboembolism, or malignancy compared to splenectomy 3
• Patients who fail one TPO-RA may still respond to the alternate agent 3

Romiplostim dosing: 1-10 µg/kg subcutaneous weekly injection 4, 5

Eltrombopag dosing: 25-75 mg oral daily dose 4

Second Choice: Splenectomy

Splenectomy should now be considered after TPO-RAs given the availability of effective medical therapy 3. It is typically deferred for at least 6-12 months to allow for potential spontaneous remission 1, 2, 3.

Splenectomy outcomes:

• Initial response rate of 80-85% 3
• Long-term durable response in 60-70% of patients over 5-10 years 1, 3
• Up to 30% of initial responders relapse within 10 years, typically within 2 years 3

Critical splenectomy risks:

• 10% surgical complication rate within 30 days, even with laparoscopic approaches 3
• 3- to 4-fold increased risk of death from septicemia, pulmonary embolism, and non-Hodgkin lymphoma that persists for >10 years 3
• Vaccination before splenectomy is essential to prevent overwhelming post-splenectomy infection 1

Third Choice: Rituximab

Rituximab is an alternative second-line option with initial response rates of 60% (40% complete response) 2, 3. However, long-term sustained responses occur in only 20-30% of cases 3. Response typically occurs within 1-8 weeks 3.

Dosing: 100 mg or 375 mg/m² weekly for 4 weeks 4

Third-Line Immunosuppressive Options for Truly Refractory Cases

When TPO-RAs, splenectomy, and rituximab have failed:

• Azathioprine 1-2 mg/kg/day (maximum 150 mg/day): response rates 45-67% 1, 3
• Cyclosporin A 2.5-3 mg/kg/day: response rates 50-80% with 42% complete response 4, 1, 3
• Mycophenolate mofetil 1000 mg twice daily: response rates up to 75% within 4-6 weeks 1, 3
• Danazol 200 mg 2-4 times daily: response rates 40-67% 1, 3
• Cyclophosphamide: response rates 24-85% but carries risk of acute myeloid leukemia 4, 3
• Dapsone 75-100 mg/day: response rates up to 50% within 3 weeks; screen for G6PD deficiency before starting 4, 3

Monitoring Requirements

• Weekly CBC with platelet counts during dose adjustment phase 1
• Monthly CBC monitoring after stable dose achieved 1, 2
• Weekly CBC for at least 2 weeks after discontinuation 1
• Assess for corticosteroid side effects, health-related quality of life, and bleeding symptoms 2

Treatment Approaches NOT Recommended

Plasmapheresis has no evidence of efficacy in chronic ITP and should not be used 1, 3.