What is the initial treatment for a patient with Immunothrombocytopenia (ITP)?

Initial Treatment for Immune Thrombocytopenia (ITP)

Corticosteroids are the standard initial treatment for newly diagnosed ITP in adults, with prednisone (0.5-2 mg/kg/day) or dexamethasone (40 mg/day for 4 days) as the preferred first-line agents. 1

Treatment Decision Framework

When to Treat

• Treatment is indicated when platelet count is <30 × 10⁹/L with bleeding symptoms, or <20 × 10⁹/L regardless of bleeding 1
• Treatment is rarely needed when platelet count exceeds 50 × 10⁹/L unless active bleeding, planned surgery, anticoagulation requirement, or high-risk profession/lifestyle exists 1
• Patients older than 60 years and those with previous hemorrhage have higher bleeding risk and may warrant earlier intervention 1

First-Line Corticosteroid Options

Prednisone Protocol:

• Dose: 0.5-2 mg/kg/day until platelet count reaches 30-50 × 10⁹/L 1
• Duration: Rapidly taper after response; discontinue by 4 weeks in non-responders to avoid corticosteroid-related complications 1
• Expected response: 60-80% initial response rate, but only 20-40% sustained response 1

Dexamethasone Protocol:

• Dose: 40 mg/day for 4 days (equivalent to 400 mg prednisone daily) 1
• Can repeat for up to 4 cycles given every 14 days 1
• Expected response: 86-90% initial response rate with 50-74% sustained response at median 8 months 1
• Advantages: Faster platelet count increase within 7 days (RR 1.31,95% CI 1.11-1.54), lower incidence of adverse events due to shorter treatment duration 1, 2

The 2019 ASH guidelines show no definitive superiority between dexamethasone and prednisone, but dexamethasone works faster and may be preferred for patients with severe thrombocytopenia and active bleeding. 1, 2

Adjunctive First-Line Therapies

IVIG (Intravenous Immunoglobulin):

• Indication: Add to corticosteroids when more rapid platelet increase is required (grade 2B recommendation) 1
• Dose: 1 g/kg as single dose; may repeat if necessary 1
• Expected response: Platelet increase within 24 hours, but effect is transient (2-4 weeks) 1
• Use as monotherapy only if corticosteroids are contraindicated 1

Anti-D Immunoglobulin:

• Indication: Alternative to IVIG in Rh(D)-positive, non-splenectomized patients if corticosteroids contraindicated 1
• Dose: 75 mcg/kg (higher than licensed 50 mcg/kg) provides response comparable to IVIG 1
• Contraindication: Avoid in autoimmune hemolytic anemia due to risk of exacerbating hemolysis 1
• Premedication: Use acetaminophen or 20 mg prednisone to reduce fever/chills 1
• Warning: Rare but serious cases of intravascular hemolysis, DIC, and renal failure reported 1

Emergency Treatment Protocol

For severe bleeding or platelet count <10 × 10⁹/L with high bleeding risk:

• Combine prednisone AND IVIG (do not switch between them—use both simultaneously) 1
• Consider high-dose methylprednisolone for rapid response 1
• Platelet transfusion may be used in combination with IVIG 1
• Emergency splenectomy is an option for life-threatening bleeding unresponsive to medical therapy 1

Critical Pitfalls to Avoid

Corticosteroid Duration:

• Never continue corticosteroids beyond 6-8 weeks for initial treatment 1
• Patients requiring on-demand corticosteroids after completing induction should be considered non-responders and switched to second-line therapy 1
• Prolonged corticosteroid use causes weight gain, cataracts, mood alterations, hypertension, infections, hyperglycemia (especially elderly), and osteoporosis 1

Rituximab in First-Line:

• The 2019 ASH guidelines suggest corticosteroids alone rather than rituximab plus corticosteroids for initial therapy (conditional recommendation) 1
• While rituximab with corticosteroids shows higher durable response (RR 1.70,95% CI 1.34-2.16) and remission (RR 1.58,95% CI 1.00-2.52), concerns about infection risk and lack of quality-of-life data limit its first-line use 1
• Consider rituximab with dexamethasone only in younger women who place high value on remission possibility over side effect concerns 1, 2

Special Populations

Pregnancy:

• Use corticosteroids or IVIG only (grade 1C recommendation) 1
• Mode of delivery should be based on obstetric indications, not maternal platelet count 1

Secondary ITP:

• HIV-associated: Treat underlying HIV with antivirals before ITP-specific therapy unless clinically significant bleeding (grade 1A) 1
• HCV-associated: Consider antiviral therapy; if ITP treatment needed, use IVIG as first-line 1
• H. pylori-positive: Administer eradication therapy (grade 1B recommendation) 1

When First-Line Fails

Patients are considered corticosteroid failures if:

• No response after 4 weeks of treatment 1
• Platelet count drops below safe levels during taper 1
• Require continuous corticosteroids to maintain platelet count 1

Second-line options include:

• Thrombopoietin receptor agonists (romiplostim, eltrombopag) 1, 3, 4
• Rituximab 1, 5
• Splenectomy 1, 5
• Fostamatinib 5, 6

The choice between second-line therapies depends on bleeding risk, patient age, desire to avoid surgery, and response urgency, but this extends beyond initial treatment scope.