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

Treatment of Immune Thrombocytopenic Purpura (ITP)

For newly diagnosed adult ITP requiring treatment, initiate corticosteroids as first-line therapy—specifically prednisone 0.5-2 mg/kg/day or high-dose dexamethasone 40 mg/day for 4 days—and add intravenous immunoglobulin (IVIg 1 g/kg) only when rapid platelet elevation is needed for active bleeding or urgent procedures. 1, 2

When to Treat

Treatment decisions should prioritize bleeding symptoms over absolute platelet counts 1, 2:

• Treatment is indicated when platelet counts are <20-30 × 10⁹/L, as bleeding risks significantly increase below this threshold 1, 3
• Treatment is also indicated for platelet counts <50 × 10⁹/L if accompanied by substantial mucous membrane bleeding 3
• Treatment is rarely indicated for platelet counts >50 × 10⁹/L unless specific risk factors exist: planned surgery, trauma risk, required anticoagulation, or platelet dysfunction 1

The goal is maintaining a hemostatic platelet count (typically 30-50 × 10⁹/L), not normalizing counts 2, 4

First-Line Treatment Options

Corticosteroids (Standard Initial Therapy)

Prednisone remains the standard first-line treatment 1, 2:

• Dose: 0.5-2 mg/kg/day until platelet count increases to 30-50 × 10⁹/L 1
• Initial response occurs in 70-80% of patients 4
• Critical caveat: Rapidly taper and discontinue after 4 weeks in non-responders to avoid corticosteroid complications 1, 2
• Prolonged use beyond 6-8 weeks should be avoided due to significant morbidities including weight gain, mood alterations, hypertension, diabetes, osteoporosis, and infection risk 4

High-dose dexamethasone offers superior sustained responses 1, 2:

• Dose: 40 mg/day for 4 days (can repeat for up to 4 cycles every 14 days) 1
• Response rates: 86-90% initial response with 50-74% achieving sustained responses lasting median 8-26 months 1, 5
• Side effects include sleeplessness, aggressive behavior, and loss of concentration, which can be unacceptably high 1
• As first-line therapy, dexamethasone produces 59% remission at 31 months; as second-line therapy, only 25% remission at 54 months 5

Adjunctive First-Line Therapies

Intravenous immunoglobulin (IVIg) 1, 2, 4:

• Dose: 1 g/kg/day for 1-2 days or 0.4 g/kg/day for 5 days 4
• Use when rapid platelet increase is needed (active bleeding, urgent procedures) or when corticosteroids are contraindicated 4
• Response occurs within 2-7 days 1

IV anti-D immunoglobulin 1, 4:

• Dose: 50-75 μg/kg 4
• Only for Rh(D) positive, non-splenectomized patients 1, 4
• Avoid in autoimmune hemolytic anemia to prevent exacerbation of hemolysis 1
• Requires blood group, DAT, and reticulocyte count before administration 1

Emergency Treatment for Life-Threatening Bleeding

For active life-threatening bleeding, combine high-dose methylprednisolone plus IVIg immediately 2:

• High-dose methylprednisolone: 30 mg/kg/day for 3 days followed by 20 mg/kg/day for 4 days 1
• Response rate: 60-100% of patients achieve platelet response within 2-7 days 1
• Consider platelet transfusion at larger-than-usual doses, possibly with IVIg 2
• Emergency splenectomy remains an option for refractory cases 1, 2

Second-Line Treatment Options

Thrombopoietin Receptor Agonists (TPO-RAs)

TPO-RAs are now the preferred second-line therapy for long-term management 2, 4:

Romiplostim (Nplate) 6:

• Dose: Starting 1 mcg/kg subcutaneously weekly, adjusted to maintain platelets 50-200 × 10⁹/L 6
• Overall platelet response rates: 88% in non-splenectomized and 79% in splenectomized patients 4, 6
• Durable response: 61% in non-splenectomized, 38% in splenectomized patients 6
• Sustained responses documented for up to 4 years with continuous administration 4
• Up to 30% of patients may achieve remission after tapering and discontinuation 4
• Important safety concern: Risk of blood clots, especially if platelet count becomes excessively high; higher risk in patients with chronic liver disease 6
• Requires weekly platelet monitoring initially, then monthly once dose is stable 6

Eltrombopag (alternative TPO-RA) 2, 4:

• Similar efficacy to romiplostim 4
• Patients who fail one TPO-RA may respond to the alternate agent 4

Critical management points for TPO-RAs 4:

• Avoid abrupt interruptions or excessive dose adjustments, which cause platelet fluctuations 4
• For patients achieving stable counts at lowest dose, consider holding therapy to monitor for potential remission 4
• Not immunosuppressive, unlike other second-line options 1

Splenectomy

Splenectomy provides long-term responses but should be delayed given availability of TPO-RAs 1, 2, 4:

• Initial response rate: 80-85% 4, 6
• Long-term durable response: 60-70% of patients maintain response over 4 years 1, 4, 6
• Response occurs within 24 hours 1
• Major risks: Postsplenectomy sepsis (rare but potentially life-threatening), permanent procedure 1, 7
• Historically the gold standard second-line therapy, now typically reserved for later in treatment algorithm 4, 3

Rituximab

Rituximab (anti-CD20 monoclonal antibody) 1, 2, 4:

• Dose: 100 mg or 375 mg/m² weekly for 4 weeks 1
• Response rates: 31-79% overall (60% in most studies), with 40% achieving complete response 1, 4
• Response occurs within 1-8 weeks of treatment initiation 4
• Long-term sustained responses: 20-30% of cases 4
• Side effects generally mild: Serum sickness, maculopapular rash, arthralgia, low-grade fever, malaise, pruritus, urticaria, throat tightness 1
• 63% of complete responders maintain response for 4-30 months 1

Third-Line Treatment Options for Chronic Refractory ITP

For patients failing first- and second-line therapies, consider the following immunosuppressive agents 1, 4:

Azathioprine 4:

• Dose: 1-2 mg/kg daily 4
• Response rate: Up to 67% 4
• Onset delayed: May take 3-6 months for effect 4

Cyclosporin A 4:

• Dose: 5 mg/kg/day initially, then 2.5-3 mg/kg/day 4
• Response rate: 50-80% 4
• Onset: 3-4 weeks 4

Mycophenolate mofetil 4:

• Dose: 1000 mg twice daily 4
• Response rate: Up to 75% 4
• Onset: 4-6 weeks 4

Danazol 4:

• Dose: 200 mg 2-4 times daily 4
• Response rate: Up to 67% 4
• Requires prolonged treatment: 3-6 months 4

Combination chemotherapy regimens 1:

• Various combinations including cyclosporin A, azathioprine, prednisone, IVIg, anti-D, vinca alkaloids, and danazol 1
• Approximately 70% achieve platelet response 1
• Consideration of carcinogenesis required with cytotoxic agents 1

Special Populations

Children with ITP

Goal is maintaining hemostatic platelet counts while minimizing prolonged corticosteroid use 1, 4:

• First-line: IVIg, IV anti-D, or short-course corticosteroids 1
• High-dose methylprednisolone (30 mg/kg/day for 3 days, then 20 mg/kg/day for 4 days) is at least as effective as IVIg 1
• Rituximab response rates: 31-68% in children with chronic refractory ITP 1
• Cytotoxic drugs should be used with extreme caution in children 1, 4
• All children with persistent or chronic ITP should be managed by an experienced pediatric hematologist 1

Pregnancy

Use corticosteroids or IVIg as first-line therapy 2:

• Mode of delivery should be based on obstetric indications, not platelet count 2

Secondary ITP

Treat underlying condition when identified 2:

• HCV-associated ITP: Consider antiviral therapy 2
• HIV-associated ITP: Treat HIV with antivirals before other ITP therapy unless significant bleeding 2
• H. pylori-positive: Eradication therapy 2

General Supportive Measures

Minimize bleeding risk through non-pharmacologic interventions 2:

• Discontinue antiplatelet agents unless absolutely necessary 2
• Control blood pressure aggressively 2
• Suppress menses in menstruating patients 2
• Consider higher target platelet counts for patients with cardiac stents requiring antiplatelet therapy 2

Common Pitfalls to Avoid

• Do not prolong corticosteroid therapy beyond 4-6 weeks in non-responders—the risks outweigh benefits 1, 4
• Do not normalize platelet counts as a treatment goal—aim for hemostatic levels (30-50 × 10⁹/L) to minimize treatment toxicity 2, 4
• Do not rush to splenectomy—TPO-RAs now offer effective, reversible second-line option with potential for remission 4
• Do not abruptly stop TPO-RAs—taper carefully to avoid rebound thrombocytopenia 4
• Do not use IV anti-D in Rh(D) negative patients or those with autoimmune hemolytic anemia 1, 4
• Do not treat based solely on platelet count—bleeding symptoms and risk factors should drive treatment decisions 1, 3