What is the recommended treatment algorithm for immune thrombocytopenia, including first‑line glucocorticoids, IVIG, second‑line rituximab or thrombopoietin‑receptor agonists, and splenectomy?

Treatment Algorithm for Immune Thrombocytopenia (ITP)

First-Line Treatment: Corticosteroids

For newly diagnosed adult ITP patients with platelet counts <30 × 10⁹/L, initiate corticosteroid therapy with either dexamethasone 40 mg daily for 4 days or prednisone 0.5-2 mg/kg/day for 2-4 weeks. 1

Dexamethasone vs. Prednisone Selection

• Dexamethasone 40 mg daily for 4 days produces initial response rates up to 90%, with sustained remission in 50-80% of patients when given as 1-4 cycles every 2-4 weeks 1
• Dexamethasone works faster than prednisone (4.7 days vs. 8.4 days to response) and appears safer with lower incidence of adverse events due to shorter treatment duration 2
• Choose dexamethasone for patients with low platelet counts and active bleeding who require rapid platelet increase 2
• Prednisone should be rapidly tapered and stopped in responders, and especially in non-responders after 4 weeks to avoid corticosteroid-related complications 1

Adding IVIG to First-Line Therapy

• Add IVIG 1 g/kg as a one-time dose when more rapid platelet increase is required beyond corticosteroids alone 1
• IVIG produces response in up to 80% of patients, with many responding within 24 hours 1
• If corticosteroids are contraindicated, use either IVIG or anti-D (in Rh-positive, non-splenectomized patients) as first-line monotherapy 1
• Anti-D 50-75 μg/kg produces similar initial response rates to IVIG but should be avoided in patients with autoimmune hemolytic anemia 1

Second-Line Treatment: After Corticosteroid Failure

For patients who fail or relapse after initial corticosteroid therapy, splenectomy remains the recommended second-line treatment. 1

Splenectomy Timing and Preparation

• Delay splenectomy for at least 12 months from diagnosis unless severe unresponsive disease or quality of life considerations mandate earlier intervention 1, 3
• Splenectomy provides 80-85% initial response rate with 60-66% sustained long-term responses 3
• Administer polyvalent pneumococcal vaccine, meningococcal C conjugate vaccine, and Haemophilus influenzae b vaccine at least 4 weeks before surgery 4
• Test for HCV and HIV before splenectomy, as these can cause secondary ITP 4
• Both laparoscopic and open splenectomy offer similar efficacy 1, 4

Critical Splenectomy Risks

• Patients face 3-fold increased risk of septicemia, 4.5-fold increased risk of pulmonary embolism, and 2.7-fold increased risk of venous thromboembolism that persists for >10 years 3
• Up to 30% of initial responders will relapse, typically within the first 2 years post-splenectomy 3
• All splenectomy patients require lifelong prophylactic antibiotics: phenoxymethylpenicillin 250-500 mg orally twice daily, or erythromycin 250-500 mg twice daily if penicillin-allergic 5
• Patients must maintain home supply of amoxicillin 3 g loading dose followed by 1 g every 8 hours for immediate use with any fever, malaise, or chills 5

Alternative Second-Line Options: Avoiding or Delaying Splenectomy

Thrombopoietin Receptor Agonists (TPO-RAs)

• TPO-RAs (romiplostim or 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 1
• TPO-RAs achieve platelet responses in 70-80% of patients 3
• TPO-RAs may be considered for patients at risk of bleeding who have failed one line of therapy (such as corticosteroids or IVIG) and have not had splenectomy, though this is a weaker recommendation 1

Rituximab

• Rituximab may be considered for patients at risk of bleeding who have failed one line of therapy such as corticosteroids, IVIG, or splenectomy 1
• Rituximab allows further delay of splenectomy while attempting medical management 3
• Dexamethasone combined with rituximab in first-line treatment produces higher response rates with better long-term results compared to dexamethasone alone, and is particularly effective in younger women 2

Treatment Thresholds and Monitoring

• Do not treat asymptomatic patients with platelet counts >30 × 10⁹/L 1
• After splenectomy, do not treat asymptomatic patients with platelet counts >30 × 10⁹/L 1
• The goal is achieving a platelet count associated with adequate hemostasis, not a normal platelet count 6

Special Populations

Pregnancy

• Pregnant patients requiring treatment should receive either corticosteroids or IVIG 1
• Mode of delivery should be based on obstetric indications, not maternal platelet count 1

Children and Adolescents

• Splenectomy should be reserved for children with chronic or persistent ITP who have significant bleeding, lack of responsiveness or intolerance to corticosteroids, IVIG, and anti-D, and/or need for improved quality of life 1
• Delay splenectomy for at least 12 months unless severe disease unresponsive to other measures 1

Common Pitfalls to Avoid

• Do not continue prednisone beyond 4 weeks in non-responders to minimize corticosteroid toxicity 1
• Do not perform bone marrow examination in patients presenting with typical ITP, as it is unnecessary regardless of age 1
• Do not assume phenoxymethylpenicillin prophylaxis covers Haemophilus influenzae after splenectomy—vaccination is essential 5
• Do not delay emergency department evaluation after initiating home antibiotics for fever in splenectomy patients, as clinical deterioration can be rapid 5
• Penicillin-resistant Streptococcus pneumoniae is emerging, yet prophylactic penicillin remains recommended despite resistance trends 5