What is the current management for Immune Thrombocytopenic Purpura (ITP) in children?

Management of Immune Thrombocytopenic Purpura (ITP) in Children

For most children with ITP, observation without treatment is the recommended approach regardless of platelet count, as long as bleeding is absent or mild, since approximately two-thirds will spontaneously remit within days to 6 months. 1, 2

Initial Assessment and Risk Stratification

Determine bleeding severity first, as this drives all treatment decisions:

• No bleeding or mild bleeding (petechiae, bruising only): Observe without treatment regardless of how low the platelet count drops 1, 2, 3
• Moderate bleeding (mucosal bleeding, epistaxis requiring intervention): Consider first-line treatment 1, 2
• Severe or life-threatening bleeding (intracranial hemorrhage, organ-threatening hemorrhage): Initiate emergency multimodal therapy immediately 1, 2, 3

Critical diagnostic considerations before assuming ITP:

• Bone marrow examination is NOT necessary for typical ITP presentation (isolated thrombocytopenia in otherwise healthy child) 2, 3
• However, if fever AND bicytopenia are present together, immediately exclude malignancy or bone marrow failure with bone marrow examination 2, 3
• Peripheral blood smear is mandatory to identify blasts or atypical cells 3

First-Line Treatment Options (for Moderate Bleeding)

When treatment is indicated, choose ONE of the following first-line options: 1, 2

Option 1: Intravenous Immunoglobulin (IVIg) - Preferred for Rapid Response

• Dose: 0.8-1 g/kg as single infusion 1, 2, 3
• Response rate: >80% of children achieve platelet response 1, 2, 3
• Time to response: 1-2 days (fastest option) 1, 3
• Side effects: Headache (can be severe), fever, nausea/vomiting 1, 3
• Duration: One-third fall below acceptable counts after 2-6 weeks 1

Use IVIg when rapid platelet increase is needed 2, 4, 3

Option 2: Short-Course Corticosteroids

• Dose: Prednisone 2-4 mg/kg/day (maximum 120 mg daily) for 5-7 days OR 4 mg/kg/day for 3-4 days 1, 2, 4
• Response rate: 72-88% achieve platelet count ≥50 × 10⁹/L within 72 hours at 4 mg/kg/day dose 2, 4, 3
• Time to response: 2-7 days 1, 4
• Side effects: Mood changes, gastritis, weight gain 1, 4
• Critical caveat: Use ONLY for 7 days or shorter to minimize toxicity; prolonged use causes growth retardation, hyperglycemia, hypertension, cataracts, behavioral abnormalities 4

Alternative corticosteroid: Dexamethasone 0.6 mg/kg/day (maximum 40 mg/day) for 4 days 4

Option 3: IV Anti-D Immunoglobulin (for Rh-Positive Children Only)

• Dose: 50-75 mcg/kg 1, 3
• Response rate: 50-77% depending on dose 1
• Time to response: ≥50% respond within 24 hours 1
• Contraindications: Do NOT use if hemoglobin already decreased from bleeding or if autoimmune hemolysis present 2, 3
• Side effects: Headache, fever, chills; mild extravascular hemolysis common; rare intravascular hemolysis and renal failure 1

Emergency Treatment for Life-Threatening Bleeding

For intracranial hemorrhage or organ-threatening bleeding, use ALL of the following simultaneously: 1, 2, 3

• Platelet transfusion: 2-3 fold larger than usual dose 2, 3
• IV methylprednisolone: 30 mg/kg/day (maximum 1 g) 1, 2, 3
• IVIg: 1 g/kg 1, 2, 3
• Consider emergency splenectomy in special circumstances 1

Never delay emergency treatment while awaiting complete diagnostic workup 3

Management of Persistent or Chronic ITP (>6 Months Duration)

Goal: Maintain hemostatic platelet count with first-line therapies and minimize prolonged corticosteroid use 1

Many children stabilize with platelet counts of 20-30 × 10⁹/L without symptoms and can continue expectant management 1

Second-Line Treatment Options (When First-Line Fails)

All children with persistent/chronic ITP should be managed by a hematologist experienced in pediatric ITP 1

High-Dose Dexamethasone

• Dose: 28-40 mg/m²/day 1, 2
• Response rate: Up to 80% achieve platelet response 1, 2
• Time to response: 3 days 1, 2
• Side effects: Sleeplessness, aggressive behavior, loss of concentration, hypertension, anxiety, gastric distress (unacceptably high) 1, 2
• Duration: Responses are short unless cycles repeated 1

High-Dose Methylprednisolone (HDMP)

• Dose: 30 mg/kg/day for 3 days followed by 20 mg/kg/day for 4 days 1, 2
• Response rate: 60-100% achieve platelet response 1, 2
• Time to response: 2-7 days 1, 2
• Note: At least as effective as IVIg but worse side-effect profile compared to prednisone 1

Rituximab

• Dose: 100 mg or 375 mg/m²/week for 4 weeks 1, 2, 3
• Response rate: 31-79% 1, 2, 3
• Time to response: Within a few weeks 1
• Sustained response: 63% achieved complete response lasting 4-30 months (variable in literature) 1, 2
• Side effects: Generally well tolerated; serum sickness, maculopapular rash, arthralgia, low-grade fever, malaise 1, 2, 3

Splenectomy

• Indications: Reserved for chronic ITP (>12 months) with significant bleeding unresponsive to other therapies 1, 2, 3
• Response rate: 60-70% long-term response 1, 2, 3
• Time to response: 24 hours 1
• Sustained response: 80% of responders maintain platelet response over 4 years 1, 2
• Major risk: Postsplenectomy sepsis 1, 2, 3
• Critical timing: Delay for at least 12 months unless severe unresponsive disease 3

Combination Regimens

• Options: Cyclosporin A, azathioprine, prednisone, IVIg, anti-D, vinca alkaloids, danazol 1
• Response rate: Approximately 70% 1
• Time to response: Days to months 1
• Critical caveat: Cytotoxic drugs should be used with EXTREME caution in children due to carcinogenesis risk 1

TPO-Receptor Agonists (Romiplostim)

• FDA-approved for pediatric patients ≥1 year with ITP for at least 6 months who have had insufficient response to corticosteroids, immunoglobulins, or splenectomy 5
• Dose: Starting at 1 mcg/kg weekly, titrated up to maximum 10 mcg/kg weekly 5
• Response rate: 52% achieved durable platelet response (≥6 weekly counts ≥50 × 10⁹/L during weeks 18-25); 71% achieved overall platelet response 5
• Note: Should NOT be used to normalize platelet counts, only to reduce bleeding risk 5

General Management Principles and Safety Measures

Activity restrictions:

• Avoid competitive contact sports with high risk of head trauma 1, 2, 3
• Other activities need not be restricted; encourage continued schooling 1, 3

Parent education:

• Provide emergency contact information and education about bleeding warning signs 2, 3
• Consider medical alert bracelet for persistent thrombocytopenia 1, 2, 3
• Family should carry card/letter with disorder details in case of emergency 1

Monitoring:

• Most children with minor/mild/moderate symptoms can be safely managed as outpatients with weekly or less-frequent visits 1
• Hospital admission reserved for clinically significant bleeding or problematic psychosocial circumstances 1

Adolescent considerations:

• Menstruation may be problematic; manage with antifibrinolytic agents and hormonal medication 1
• Lifestyle and self-image issues assume greater importance and should influence treatment decisions 1

Common Pitfalls to Avoid

• Do NOT treat children with platelet counts >30 × 10⁹/L and no symptoms or only minor purpura - observation is appropriate 3
• Do NOT use corticosteroid courses longer than 7 days for initial treatment - increases toxicity without improving outcomes 4
• Do NOT perform bone marrow examination in typical ITP cases unless atypical features present 2, 3
• Do NOT use anti-D if hemoglobin already decreased from bleeding 2, 3
• Do NOT forget that intracranial hemorrhage risk is only 0.1-0.5% - treatment risks may exceed disease risks 1, 3, 6
• Do NOT assume treatment changes long-term outcome - treatments raise platelet counts but do not influence ultimate remission 6, 7