What are the treatment options for Immune Thrombocytopenic Purpura (ITP)?

Treatment of Immune Thrombocytopenic Purpura (ITP)

For newly diagnosed adult ITP requiring treatment, initiate corticosteroids (prednisone 0.5-2 mg/kg/day or high-dose dexamethasone) as first-line therapy, adding intravenous immunoglobulin (IVIg 1 g/kg) when rapid platelet elevation is needed for bleeding risk or urgent procedures. 1, 2

When to Treat

Treatment is indicated based on bleeding risk, not platelet count alone:

• Treat when platelet count <20-30 × 10⁹/L regardless of bleeding symptoms 3
• Treat at higher counts (30-50 × 10⁹/L) if substantial mucous membrane bleeding is present 3
• Treat for active CNS, GI, or genitourinary bleeding at any platelet count 4
• Observation is appropriate for asymptomatic patients with counts >30 × 10⁹/L 3

First-Line Treatment Options

Corticosteroids (Primary First-Line)

Prednisone is the standard initial therapy:

• Dose: 0.5-2 mg/kg/day until platelet count increases 1
• Rapidly taper and discontinue after 4 weeks in non-responders to avoid corticosteroid complications 1
• Never continue beyond 6-8 weeks as initial treatment 4
• Initial response occurs in 60-80% of patients, but sustained responses only in 20-40% 4

High-dose dexamethasone offers superior initial response:

• Response rates up to 90% with sustained responses in 50-80% of patients 1
• Administered in 1-4 cycles 1

High-dose methylprednisolone (HDMP):

• Response rates as high as 95% with faster response times 1
• Particularly useful in emergency settings 4

Intravenous Immunoglobulin (IVIg)

Add IVIg when rapid platelet increase is required (within 24 hours):

• Dose: 1 g/kg as single dose over 1-2 days (preferred) or 0.4 g/kg/day for 5 days 4, 1, 2
• Response rate up to 80%, with many responding within 24 hours 1
• Critical caveat: Rare but serious toxicities include renal failure and thrombosis 4
• Concomitant corticosteroids may enhance IVIg response and reduce infusion reactions 4

Emergency Treatment for Active Bleeding

For life-threatening bleeding, combine prednisone and IVIg immediately 4:

• High-dose methylprednisolone plus IVIg is the recommended combination 4
• Consider platelet transfusion at larger-than-usual doses, possibly with IVIg 4, 1
• Emergency splenectomy remains an option for refractory cases 4
• Vinca alkaloids show evidence of rapid response 4

Second-Line Treatment Options

Thrombopoietin Receptor Agonists (TPO-RAs)

TPO-RAs are recommended for patients who fail corticosteroids and have bleeding risk 2:

Romiplostim (Nplate):

• Durable platelet response in 61% of non-splenectomized and 38% of splenectomized patients 5
• Overall response rates: 88% (non-splenectomized) and 79% (splenectomized) 5
• Dose: Start 1 mcg/kg subcutaneously weekly, adjust to maintain platelets 50-200 × 10⁹/L 5
• Significant advantage: Reduced need for rescue therapy (20% vs 62% placebo in non-splenectomized) 5

Eltrombopag (oral alternative):

• Similar efficacy to romiplostim 4
• Allows early switch from prolonged corticosteroids, improving clinical benefits 4

Splenectomy

Splenectomy provides long-term responses in 60-70% of patients 1, 2:

• Initial response rate: 85%, but durable responses in 60-65% 4
• Relapse occurs in 20-30% of responders, especially within 2 years 4
• Critical caveat: 10% develop short-term or long-term complications 4
• Rare risk of life-threatening infections at any time post-splenectomy 3
• Recommended for patients who fail corticosteroid therapy 2

Rituximab

Rituximab (anti-CD20 monoclonal antibody):

• Response rates: 31-79%, with 60% overall and 40% complete response 4, 1
• Dose: 375 mg/m² weekly × 4 (lower doses may be effective) 4
• Time to response: 1-8 weeks 4
• Critical caveats: Risk of hepatitis B reactivation and progressive multifocal leukoencephalopathy, especially with concurrent immunosuppression 4
• Reduces vaccine efficacy during treatment 4

Other Immunosuppressive Agents

The American Society of Hematology consensus provides response rates for additional second-line options 4:

• Azathioprine 1-2 mg/kg: Response in up to 67%, but slow (3-6 months) 4
• Cyclosporin A 2.5-3 mg/kg: 50-80% response in 3-4 weeks 4
• Mycophenolate mofetil 1000 mg twice daily: Up to 75% response in 4-6 weeks 4
• Dapsone 75-100 mg: Up to 50% response in 3 weeks; screen for G6PD deficiency first 4
• Danazol 200 mg 2-4 times daily: 67% response but takes 3-6 months 4

Treatment Algorithm

Newly diagnosed ITP with bleeding or platelets <20-30 × 10⁹/L:

1. Start prednisone 0.5-2 mg/kg/day or high-dose dexamethasone 1
2. Add IVIg 1 g/kg if rapid response needed 1, 2
3. If no response by 4 weeks, discontinue corticosteroids 1

Failed first-line therapy:

1. Consider TPO-RA (romiplostim or eltrombopag) for ongoing bleeding risk 2
2. Alternative: Rituximab if patient prefers to avoid splenectomy 1
3. Splenectomy for definitive therapy in appropriate candidates 2

Refractory after splenectomy or contraindication to splenectomy:

1. TPO-RA as preferred option 2
2. Consider other immunosuppressive agents based on patient factors 4

Special Populations

Pregnancy:

• Use corticosteroids or IVIg as first-line 1, 2
• Mode of delivery based on obstetric indications, not platelet count 2

Secondary ITP:

• HCV-associated: Consider antiviral therapy 2
• HIV-associated: Treat HIV with antivirals before other ITP therapy unless significant bleeding 2
• H. pylori-positive: Eradication therapy recommended 1, 2

General Supportive Measures

• Discontinue antiplatelet agents (aspirin, NSAIDs, clopidogrel) unless absolutely necessary 4
• Control blood pressure aggressively 4
• Suppress menses in menstruating patients 4
• Exception: Patients with cardiac stents requiring antiplatelet therapy need higher target platelet counts 4

Critical Monitoring

• Weekly platelet counts during dose adjustment phase 5
• Monthly platelet counts once stable dose achieved 5
• Monitor for at least 2 weeks after discontinuing treatment to detect rebound thrombocytopenia 5
• Watch for bone marrow changes (increased reticulin) with TPO-RA therapy 5