What are the treatment options for idiopathic thrombocytopenic purpura (ITP)?

Treatment of Idiopathic Thrombocytopenic Purpura (ITP)

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

First-Line Treatment Options

Corticosteroids

• Prednisone remains the standard initial therapy at 0.5-2 mg/kg/day until platelet count increases, then rapidly taper and discontinue after 4 weeks in non-responders to avoid corticosteroid complications. 1
• Randomized trials demonstrate that prednisone increases platelet counts more quickly than no treatment, with median time to achieve platelet count >50,000/μL of 4 days versus 16 days in untreated children. 3
• High-dose dexamethasone (28-40 mg/m²/day for 4 days, repeated every 4 weeks for up to 6 cycles) offers superior initial response rates up to 90% with sustained responses in 50-80% of patients. 3, 1
• High-dose methylprednisolone (30 mg/kg/day for 3 days followed by 20 mg/kg/day for 4 days) is at least as effective as IVIg, with 60-100% of patients achieving platelet response within 2-7 days. 3

Intravenous Immunoglobulin (IVIg)

• IVIg should be added when more rapid platelet count increase is required, administered as 1 g/kg as a one-time dose that may be repeated if necessary. 2
• IVIg is particularly useful for stimulating rapid platelet increases before planned procedures or in patients with significant mucous membrane bleeding. 4

Observation Without Treatment

• Many studies suggest 30-70% of children recover from severe thrombocytopenia, achieving platelet counts of 50,000-100,000/μL within 3 weeks without specific treatment. 3
• Treatment should be based on bleeding risk, not platelet count alone—bleeding symptoms should be the rationale for treatment. 4

Emergency Treatment for Life-Threatening Bleeding

For life-threatening bleeding, combine high-dose parenteral glucocorticoid (30 mg/kg methylprednisolone daily for 3 days), IVIg, and platelet transfusions, either alone or in combination. 3, 1

• Platelet transfusions should be given at larger-than-usual doses, possibly with IVIg. 1
• Emergency splenectomy remains an option for refractory cases with severe, life-threatening hemorrhage. 3, 1

Indications for Treatment

Adults

• Treatment is indicated for patients with platelet counts <20,000-30,000/μL, as bleeding risks are significantly greater at these levels. 4
• For platelet counts higher but still <50,000/μL, treatment is indicated if accompanied by substantial mucous membrane bleeding. 4

Children

• Hospitalization is appropriate for children with severe, life-threatening bleeding regardless of platelet count, and for children with platelet count <20,000/μL and mucous membrane bleeding requiring clinical intervention. 3
• Hospitalization is inappropriate for children with platelet count 20,000-30,000/μL who are asymptomatic, or for children with platelet count >30,000/μL who are either asymptomatic or have only minor purpura. 3

Second-Line Treatment Options

Splenectomy

• Splenectomy is recommended for patients who have failed corticosteroid therapy and provides long-term responses in 60-70% of patients with an initial response rate of 85%. 1, 2
• Splenectomy remains the gold standard for definitive treatment, producing complete clinical cure in 70-80% of cases with very low operative risk. 5
• Common pitfall: Physicians and patients are increasingly reluctant to pursue splenectomy due to rare but life-threatening infection risks and the invasive nature of the procedure. 4

Thrombopoietin Receptor Agonists (TPO-RAs)

• TPO-RAs (romiplostim and eltrombopag) are recommended for patients at risk of bleeding who relapse after splenectomy or have contraindications to splenectomy and have failed at least one other therapy. 2
• Romiplostim is administered subcutaneously once weekly with individual dose adjustments to maintain platelet counts 50,000-200,000/μL. 6
• In placebo-controlled studies, romiplostim achieved durable platelet response in 61% of non-splenectomized patients and 38% of splenectomized patients versus 5% and 0% with placebo, respectively. 6
• Warning: Romiplostim may cause dangerous increases in platelet count leading to blood clots, including potentially fatal complications such as pulmonary embolism, heart attacks, or strokes. 6

Rituximab

• Rituximab (375 mg/m²/week for 4 weeks or 100 mg weekly) achieves response rates of 31-79% in children and approximately 50% short-term response with >30% sustained response in adults. 3, 7
• Rituximab is probably the single most effective agent and least toxic when splenectomy fails. 7
• Generally well tolerated with mild side effects including serum sickness, rash, arthralgia, low-grade fever, and malaise. 3

Other Immunosuppressive Agents

• Cytotoxic or other immunosuppressive agents (cyclophosphamide, azathioprine, vinca alkaloids, danazol) should be reserved for patients with severe disease refractory to both splenectomy and rituximab. 7
• These agents have limited clinical usefulness and are burdened by severe side effects—they should not be used as primary therapy. 5, 8
• Vinca alkaloids show 63% response rate but with significant toxicity requiring discontinuation in some patients. 8
• Azathioprine shows 45% response rate with 9% remission but requires at least one month to observe response. 8

Special Populations

Pregnancy

• Pregnant patients requiring treatment should receive either corticosteroids or IVIg as first-line therapy. 2
• Mode of delivery should be based on obstetric indications rather than platelet count. 1, 2

Secondary ITP

• For HCV-associated ITP, consider antiviral therapy in the absence of contraindications. 2
• For HIV-associated ITP, treat HIV infection with antiviral therapy before other treatment options unless clinically significant bleeding is present. 1, 2
• For H. pylori-positive patients, eradication therapy is recommended. 1, 2

General Supportive Measures

• Discontinue antiplatelet agents unless absolutely necessary. 1
• Control blood pressure aggressively to reduce bleeding risk. 1
• Suppress menses in menstruating patients with significant thrombocytopenia. 1
• Consider higher target platelet counts for patients with cardiac stents requiring antiplatelet therapy. 1

Monitoring Requirements

• Weekly platelet count monitoring during dose adjustment phase, then monthly once stable dose achieved. 6
• After stopping treatment, monitor platelet counts for at least 2 weeks to check for rebound thrombocytopenia. 6
• Bone marrow examination is not necessary for patients presenting with typical ITP. 2