What is the recommended management approach for chronic immune thrombocytopenia in adults?

Management of Chronic Immune Thrombocytopenia in Adults

For adults with chronic ITP who have failed or are intolerant to corticosteroids, splenectomy or thrombopoietin receptor agonists (TPO-RAs) are the recommended second-line options, with TPO-RAs increasingly preferred in modern practice due to excellent efficacy and avoidance of surgical risks. 1

Initial Assessment and Treatment Thresholds

• Treatment is indicated only when platelet counts fall below 30 × 10⁹/L with bleeding risk or below 50 × 10⁹/L in patients requiring anticoagulation, undergoing procedures, or with comorbidities that increase bleeding risk. 1
• The goal is not to normalize platelet counts but to maintain counts ≥50 × 10⁹/L sufficient to prevent clinically significant bleeding. 1, 2
• Asymptomatic patients with platelet counts ≥30 × 10⁹/L can be safely observed without treatment. 1

Second-Line Treatment Options After Corticosteroid Failure

Thrombopoietin Receptor Agonists (Preferred in Modern Practice)

TPO-RAs are recommended for patients at risk of bleeding who have failed corticosteroids, with or without prior splenectomy. 1

• Romiplostim (subcutaneous): Start at 1 mcg/kg weekly, titrate by 1 mcg/kg increments to achieve platelet count ≥50 × 10⁹/L, maximum dose 10 mcg/kg weekly. 2
• Eltrombopag (oral): Alternative TPO-RA with similar efficacy. 3, 4
• Avatrombopag (oral): Newer TPO-RA approved for chronic ITP with favorable safety profile. 4

Advantages of TPO-RAs:

• Response rates of 70–90% in corticosteroid-refractory patients. 3
• Avoid surgical risks and lifelong asplenia complications. 3
• Can be discontinued after sustained response in some patients. 3

Monitoring requirements:

• Weekly CBC during dose titration, then monthly once stable dose established. 2
• Weekly CBC for 2 weeks after discontinuation to detect rebound thrombocytopenia. 2

Splenectomy

Splenectomy remains a definitive option for patients who have failed corticosteroids and is recommended by ASH guidelines with grade 1B evidence. 1

• Laparoscopic and open splenectomy offer similar efficacy (grade 1C). 1
• Response rates of 60–70% with durable remissions in many patients. 3
• Mandatory vaccinations (pneumococcal, meningococcal, Haemophilus influenzae type b) must be administered ≥2 weeks before splenectomy. 1

Defer splenectomy for at least 12 months from diagnosis unless severe unresponsive disease or quality-of-life considerations mandate earlier intervention. 1

Risks to discuss:

• Lifelong infection risk (overwhelming post-splenectomy sepsis). 3
• Thrombotic complications. 3
• Surgical morbidity. 3

Rituximab

Rituximab may be considered for patients at bleeding risk who have failed corticosteroids, IVIg, or splenectomy (grade 2C). 1

• Response rates of 40–60% but durability is variable. 3
• Typically given as 375 mg/m² weekly × 4 doses. 3
• Consider in patients who decline splenectomy or have contraindications to TPO-RAs. 3

Third-Line and Refractory Disease Management

For patients who fail splenectomy or have contraindications, TPO-RAs are strongly recommended (grade 1B). 1

Alternative immunosuppressive agents for refractory cases include:

• Fostamatinib (tyrosine kinase inhibitor, FDA-approved). 3
• Azathioprine, cyclophosphamide, cyclosporine, mycophenolate mofetil. 3
• Danazol, dapsone, Vinca alkaloids. 3

These agents have lower response rates (30–50%) and significant toxicity profiles; reserve for patients unresponsive to standard therapies. 3

Treatment Algorithm for Chronic ITP

1. Confirm chronic ITP diagnosis (thrombocytopenia persisting >12 months, exclusion of secondary causes including HIV, HCV, H. pylori). 1

2. Assess bleeding risk and platelet count:

   • Platelet count ≥30 × 10⁹/L with no bleeding → Observation
   • Platelet count <30 × 10⁹/L or bleeding → Initiate treatment

3. First-line treatment (if not already given):

   • Longer-course corticosteroids (prednisone 1–2 mg/kg/day for 2–4 weeks, then taper). 1
   • Add IVIg 1 g/kg if rapid response needed. 1

4. Second-line treatment (corticosteroid failure/intolerance):

   • Preferred: TPO-RA (romiplostim, eltrombopag, or avatrombopag). 1, 2, 3, 4
   • Alternative: Splenectomy (defer ≥12 months if possible). 1
   • Alternative: Rituximab. 1

5. Third-line treatment (post-splenectomy failure or contraindication):

   • TPO-RA if not already tried. 1
   • Fostamatinib or other immunosuppressive agents. 3

Critical Pitfalls to Avoid

• Never attempt to normalize platelet counts—this increases treatment toxicity without improving outcomes. 1, 2
• Do not continue ineffective therapy beyond 4 weeks at maximum dose—switch to alternative agents. 2
• Do not perform splenectomy without confirming ITP diagnosis via bone marrow examination in patients >60 years, those with systemic symptoms, or atypical features. 1, 5
• Do not omit mandatory infectious disease testing (HIV, HCV, H. pylori) before labeling ITP as "primary." 1
• Avoid prolonged corticosteroid courses (>6 weeks) due to substantial morbidity including osteoporosis, diabetes, hypertension, and avascular necrosis. 1, 6

Quality of Life and Morbidity Considerations

• TPO-RAs preserve quality of life by avoiding surgery and allowing dose adjustments based on lifestyle needs (e.g., temporary dose increases before high-risk activities). 3
• Splenectomy offers potential cure but imposes lifelong infection risk and may not be reversible if ineffective. 3
• Refractory ITP in adolescents and young adults (14% at 48 months) is associated with high disease burden, lower platelet counts, and more bleeding—early escalation to TPO-RAs or splenectomy is warranted. 7

Monitoring and Follow-Up

• Monthly platelet counts once stable on TPO-RA therapy. 2
• Assess for treatment response at 4 weeks—if no improvement, escalate therapy. 2
• Screen for secondary causes if disease behavior changes (new cytopenias, organomegaly, systemic symptoms). 1
• Bone marrow examination mandatory before splenectomy in chronic ITP to exclude myelodysplastic syndrome or other marrow pathology. 1, 5