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 as first-line therapy—specifically prednisone 0.5-2 mg/kg/day or high-dose dexamethasone 40 mg/day for 4 days—and add intravenous immunoglobulin (IVIg 1 g/kg) only when rapid platelet elevation is needed for active bleeding or urgent procedures. 1, 2

When to Initiate Treatment

Treatment decisions should prioritize bleeding symptoms over absolute platelet counts, with the following indications: 1

• Platelet counts <20-30 × 10⁹/L warrant treatment as bleeding risks significantly increase below this threshold 1
• Active bleeding or substantial mucous membrane bleeding at any platelet count 3
• Planned invasive procedures requiring hemostatic platelet levels 4

The treatment goal is maintaining a hemostatic platelet count (typically 30-50 × 10⁹/L), not normalizing counts. 1, 5

First-Line Treatment Options

Corticosteroids

Prednisone is the standard initial therapy: 2

• Dose: 0.5-2 mg/kg/day until platelet count increases 1, 2
• Initial response occurs in 70-80% of patients, but sustained responses only in 20-40% 5
• Rapidly taper and discontinue after 4 weeks in non-responders to avoid complications 2
• The American College of Physicians recommends against prolonged corticosteroid therapy beyond 4-6 weeks 1

High-dose dexamethasone offers superior initial response: 2

• Dose: 40 mg/day for 4 days 1, 2
• Response rates up to 90% with sustained responses in 50-80% of patients 2
• Can be administered in 1-4 cycles 2

Common pitfall: Prolonged corticosteroid use causes significant side effects including weight gain, mood alterations, hypertension, diabetes, osteoporosis, and increased infection risk. 5 Avoid extending treatment beyond 6-8 weeks. 5

Intravenous Immunoglobulin (IVIg)

IVIg should be reserved for specific situations: 4, 1

• When rapid platelet increase is required (works within 2-7 days) 4
• Active bleeding requiring immediate intervention 4
• Urgent procedures 1, 2
• Corticosteroid contraindications or significant side effects 4

Dosing: 4

• 0.4 g/kg/day for 5 days, OR
• 1 g/kg/day for 1-2 days (single dose preferred) 4
• Raises platelet count in >80% of patients 4

IV Anti-D Immunoglobulin

For Rh(D)-positive, non-splenectomized patients: 4

• Dose: 50-75 μg/kg 4, 5
• Effective and well-tolerated 4
• Mild extravascular hemolysis is common; rare cases of severe intravascular hemolysis reported 4
• Monitor for neonatal jaundice and anemia if used in pregnancy 4

Emergency Treatment for Life-Threatening Bleeding

For organ- or life-threatening bleeding, combine multiple therapies immediately: 4, 2

1. High-dose methylprednisolone PLUS IVIg (recommended combination) 2, 6
2. Platelet transfusion at 2-3 fold larger-than-usual doses 4, 2
3. Emergency splenectomy remains an option for refractory cases 2

This combined approach produces rapid platelet increases within 12-24 hours, with 9/11 patients achieving counts ≥30 × 10⁹/L within 12 hours in one study. 6

Second-Line Treatment Options

Thrombopoietin receptor agonists (TPO-RAs) are the preferred second-line therapy for long-term management of ITP. 1, 5

TPO-Receptor Agonists (Romiplostim, Eltrombopag)

• Overall platelet response rates: 88% in non-splenectomized, 79% in splenectomized patients 5
• Sustained responses documented for up to 4 years with continuous administration 5
• Up to 30% of patients may achieve remission after tapering and discontinuation 5
• Patients who fail one TPO-RA may respond to the alternate agent 5

Romiplostim (Nplate) dosing: 7

• Starting dose: 1 mcg/kg subcutaneously weekly
• Median effective dose: 2-3 mcg/kg weekly (non-splenectomized), 3 mcg/kg weekly (splenectomized) 7
• Adjust dose to maintain platelet counts 50-200 × 10⁹/L 7
• Durable response achieved in 61% of non-splenectomized and 38% of splenectomized patients 7

Critical warnings for TPO-RAs: 7

• Risk of thrombosis, especially if platelet count becomes excessively high
• Increased reticulin in bone marrow (may improve after discontinuation)
• Avoid abrupt interruptions or excessive dose adjustments to prevent platelet fluctuations 5

Splenectomy

• Initial response rate: 80-85% 1
• Long-term durable response: 60-70% maintain response over 4 years 1, 5
• Should be delayed given availability of TPO-RAs 1
• Best performed in second trimester if needed during pregnancy 4
• Requires appropriate vaccination during or after procedure 4

Common pitfall: Historically considered gold standard, but splenectomy is invasive, permanent, and carries risk of life-threatening infections. 3 TPO-RAs now offer effective alternative. 1, 5

Rituximab

• Response rates: 31-79% overall, 40% complete response 1
• Long-term sustained responses: 20-30% of cases 1, 5
• Response typically occurs within 1-8 weeks 5

Third-Line Treatment Options

For patients failing first- and second-line therapies: 5

• Azathioprine: 1-2 mg/kg daily; response in up to two-thirds, but takes 3-6 months 5
• Cyclosporin A: 5 mg/kg/day initially, then 2.5-3 mg/kg/day; 50-80% response within 3-4 weeks 5
• Cyclophosphamide: 1-2 mg/kg orally daily or 0.3-1 g/m² IV every 2-4 weeks; 24-85% response 5
• Mycophenolate mofetil: 1000 mg twice daily; up to 75% response within 4-6 weeks 5

Special Populations

Pregnancy

Use corticosteroids or IVIg as first-line therapy in pregnant patients: 4, 1, 2

• Prednisone: 10-20 mg/day initially, adjusted to minimum effective dose 4
• Short-term, low-dose prednisone is generally safe for mother and fetus 4
• IVIg if corticosteroids ineffective or significant side effects occur 4
• IV anti-D (50-75 μg/kg) safe in second and third trimesters for Rh(D)-positive patients 4

Mode of delivery should be based on obstetric indications, not platelet count. 1, 2 Cesarean section is NOT safer for the fetus with thrombocytopenia than uncomplicated vaginal delivery. 4

Neonatal considerations: 4

• Neonatal mortality rate <1% in babies born to mothers with ITP 4
• Severe neonatal thrombocytopenia occurs in 8.9-14.7% 4
• Intracranial hemorrhage in 0-1.5% of infants with neonatal thrombocytopenia 4

Children (≥1 Year Old)

The goal is maintaining hemostatic platelet counts while minimizing prolonged corticosteroid use: 4, 1

First-line options: 4

• IVIg: 0.8-1 g/kg single dose (raises count in >80% within 2-7 days) 4
• IV anti-D: For Rh(D)-positive children 4
• Prednisone: 1-2 mg/kg/day OR high-dose 4 mg/kg/day for 3-4 days (72-88% response within 72 hours) 4

Important consideration: Approximately two-thirds of children improve spontaneously within days to 6 months. 4 Many children stabilize with platelet counts of 20-30 × 10⁹/L without symptoms and can be managed expectantly. 4

Emergency treatment in children: 4

• 2-3 fold larger-than-usual platelet dose
• High-dose IV corticosteroids
• IVIg or IV anti-D 4

Secondary ITP

Treat the underlying condition first: 1, 2

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

General Supportive Measures

Minimize bleeding risk through non-pharmacologic interventions: 1, 2

• Discontinue antiplatelet agents unless absolutely necessary 1, 2
• Control blood pressure aggressively 1, 2
• Suppress menses in menstruating patients (use antifibrinolytic agents and hormonal medication) 4, 1, 2
• Consider higher target platelet counts (>50 × 10⁹/L) for patients with cardiac stents requiring antiplatelet therapy 1, 2
• Medical alert identification advisable for children and adults with chronic ITP 4