What are the treatment options for Immune Thrombocytopenic Purpura (ITP)?

Treatment of Immune Thrombocytopenic Purpura (ITP)

Corticosteroids are the standard first-line therapy for ITP, with prednisone 0.5-2 mg/kg/day or high-dose dexamethasone providing initial response rates of 70-90%, though sustained remissions occur in only 20-50% of patients. 1, 2

First-Line Treatment Options

Corticosteroid Regimens

Prednisone remains the primary initial therapy at 0.5-2 mg/kg/day until platelet count increases, typically within several days to weeks 1. The American Society of Hematology emphasizes that corticosteroids should be rapidly tapered and stopped in responders, and especially in non-responders after 4 weeks to avoid corticosteroid-related complications including weight gain, mood alterations, hypertension, diabetes, osteoporosis, and increased infection risk 1, 2.

High-dose dexamethasone demonstrates superior initial response rates of 86-90% with sustained responses in 50-80% of patients when given in 1-4 cycles 1, 3. When used as first-line treatment, 59% of patients remained in remission after 31 months, though as second-line therapy only 25% maintained remission after 54 months 3. Side effects include sleeplessness, aggressive behavior, and loss of concentration, which can be unacceptably high 4.

High-dose methylprednisolone (HDMP) at 30 mg/kg/day for 3 days followed by 20 mg/kg/day for 4 days achieves response rates as high as 95% with faster response times compared to standard prednisone 4, 1. This regimen is at least as effective as IVIg with responses occurring within 2-7 days, though it has a worse side-effect profile compared to prednisone 4.

Rapid-Response Agents

Intravenous immunoglobulin (IVIg) produces rapid responses in up to 80% of patients, with many responding within 24 hours 1, 5. The recommended dosing is 1 g/kg as a one-time dose (may be repeated if necessary) rather than the historical 0.4 g/kg/day for 5 days 4, 5. IVIg is particularly useful when rapid platelet count increase is required before procedures or in emergency settings 1, 5. Rare but serious toxicities include renal failure and thrombosis 4.

IV anti-D immunoglobulin at 50-75 μg/kg can be used for Rh(D) positive, non-splenectomized patients as an alternative first-line option 2.

Emergency Treatment for Severe Bleeding

For patients with uncontrolled bleeding, active CNS, GI, or genitourinary bleeding, combine prednisone with IVIg as the recommended emergency treatment. 4, 1 High-dose methylprednisolone may also be useful in this setting 4. Platelet transfusions at larger-than-usual doses, possibly in combination with IVIg, and emergency splenectomy should be considered for life-threatening situations 4, 1. There is evidence of rapid response to vinca alkaloids as well 4.

Second-Line Treatment Options

Thrombopoietin Receptor Agonists (TPO-RAs)

TPO-RAs are now the preferred second-line therapy for long-term management of chronic ITP, with overall platelet response rates of 88% in non-splenectomized and 79% in splenectomized patients. 2 Romiplostim demonstrated durable platelet responses with 61% of non-splenectomized patients and 38% of splenectomized patients achieving sustained responses over 24 weeks 6. Sustained responses for up to 4 years with continuous administration have been documented, with potential for remission in up to 30% of patients after tapering and discontinuation 2.

Critical pitfall: Abrupt interruptions of TPO-RAs or excessive dose adjustments may cause platelet fluctuations and should be avoided, especially in patients with a history of splenectomy 2. Patients who do not respond to one TPO-RA may respond to the alternate TPO-RA 2. The FDA label warns that excessive dosing may cause dangerous increases in platelet count leading to thrombotic complications, including blood clots in the liver in patients with chronic liver disease 6.

Rituximab

Rituximab (anti-CD20 monoclonal antibody) at 375 mg/m² weekly for 4 weeks achieves response rates of 31-79%, with complete responses in 40% of patients 4, 2. Response typically occurs within 1-8 weeks of treatment initiation, with long-term responses documented in 20-30% of cases 4, 2. Lower doses (100 mg weekly) may also be effective 4. Side effects are generally mild and easily resolved, including serum sickness, maculopapular rash, arthralgia, low-grade fever, malaise, pruritus, urticaria, and throat tightness 4.

Splenectomy

Splenectomy provides long-term responses in 60-70% of patients with initial response rates of 80%, and 80% of responders maintain platelet response over 4 years 4, 1, 5. Response occurs within 24 hours 4. However, postsplenectomy complications include life-threatening sepsis that may occur at any time after the procedure 4, 5. The American Society of Hematology recommends splenectomy for patients who have failed corticosteroid therapy 5.

Third-Line Treatment Options

For patients failing first- and second-line therapies, multiple immunosuppressive agents are available:

• Azathioprine 1-2 mg/kg daily achieves responses in up to two-thirds of patients but requires 3-6 months for effect 4, 2
• Cyclosporin A 5 mg/kg/day initially (titrated to blood levels 100-200 ng/mL) shows response rates of 50-80% within 3-4 weeks 4, 2
• Cyclophosphamide 1-2 mg/kg orally daily or 0.3-1 g/m² IV produces responses in 24-85% of patients within 1-16 weeks 4, 2
• Danazol 200 mg 2-4 times daily achieves responses in up to 67% of patients but requires 3-6 months of treatment 4, 2
• Dapsone 75-100 mg daily shows responses in up to 50% of patients within 3 weeks 4, 2
• Mycophenolate mofetil 1000 mg twice daily achieves responses in up to 75% of patients within 4-6 weeks 4, 2

Treatment Algorithm and Key Principles

Treatment decisions should be based on bleeding severity, bleeding risk, and patient activity level rather than platelet count alone. 2 The goal is to maintain a hemostatic platelet count (typically >30-50 × 10⁹/L) rather than normalizing platelet counts 2, 5.

For newly diagnosed ITP:

1. Start with corticosteroids (prednisone or high-dose dexamethasone) 1, 2
2. Add IVIg if rapid platelet increase is needed 1, 5
3. Taper corticosteroids rapidly; discontinue after 4 weeks in non-responders 1, 2

For persistent/chronic ITP after first-line failure:

1. Consider TPO-RAs as preferred second-line therapy 2
2. Alternative options include rituximab or splenectomy 2, 5
3. Reserve third-line immunosuppressive agents for refractory cases 4, 2

Critical pitfall: Prolonged corticosteroid use (>6-8 weeks) should be avoided due to significant side effects, and patients requiring on-demand administration of corticosteroids after completing first-line treatment should be considered non-responders and promptly switched to second-line therapy 2.

Special Populations

In pregnancy, corticosteroids or IVIg are recommended first-line treatments, with mode of delivery based on obstetric indications rather than platelet count 5.

In children, the treatment approach is similar to adults but with more caution regarding long-term corticosteroid use 1, 5. Cytotoxic drugs should be used with extreme caution in children 4, 2. All children with persistent or chronic ITP should have their case reviewed and managed by a hematologist experienced in pediatric ITP 4.

In secondary ITP, address the underlying cause: treat HCV or HIV infection with antiviral therapy before other treatments unless clinically significant bleeding is present, and provide H. pylori eradication therapy if detected 1, 5.