What is the recommended treatment strategy for immune thrombocytopenia (ITP) based on platelet count and bleeding severity?

Treatment of Immune Thrombocytopenia (ITP)

Initial Management Decision: Observation vs. Treatment

The decision to treat ITP should be based on bleeding severity and risk, not platelet count alone—patients with no bleeding or only mild skin manifestations (petechiae, bruising) should be managed with observation regardless of platelet count. 1

When Treatment is NOT Required:

• Asymptomatic patients or those with isolated skin findings (petechiae, bruising only) 1
• Platelet count > 30 × 10⁹/L without bleeding symptoms 1
• Post-splenectomy patients with platelets > 30 × 10⁹/L who are asymptomatic 1

When Treatment IS Required:

• Active mucosal bleeding (oral, nasal, gastrointestinal, genitourinary) 1
• Severe thrombocytopenia with bleeding risk factors (hypertension, advanced age, anticoagulation need) 1
• Need for invasive procedures 2
• Quality of life significantly impaired (e.g., heavy menstrual bleeding causing iron deficiency) 1

Critical caveat: Bleeding risk increases at platelet counts < 20-30 × 10⁹/L, but this threshold alone does not mandate treatment in asymptomatic patients. 1

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First-Line Treatment for Adults

For adults requiring treatment, longer courses of corticosteroids (prednisone 1 mg/kg daily for 21 days then tapered) are recommended over short courses or IVIg because they provide longer duration of response. 1

First-Line Options (in order of preference based on clinical context):

1. Corticosteroids (preferred for sustained response):

   • Prednisone 1 mg/kg orally daily for 21 days, then taper 1
   • Alternative: Dexamethasone 40 mg orally for 4 days (shorter course, less durable) 1

2. Intravenous Immunoglobulin (IVIg) (preferred when rapid platelet rise needed):

   • Dose: 0.8-1 g/kg as single infusion 1
   • Use when faster platelet increase required (e.g., pre-procedure, active bleeding) 1

3. Anti-D Immunoglobulin (for Rh-positive, non-splenectomized patients only):

   • Only in Rh-positive patients with intact spleen 1
   • Contraindicated if hemoglobin already decreased from bleeding or evidence of autoimmune hemolysis 1

Key distinction: IVIg provides the most rapid platelet response (days), followed by high-dose dexamethasone (days to week), then prednisone (1-2 weeks), but longer corticosteroid courses provide more durable responses. 1, 3

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First-Line Treatment for Children

Children with no bleeding or only skin manifestations should be observed without treatment, regardless of platelet count. 1

When Pediatric Treatment is Required:

First-line options (equal preference):

• Single dose IVIg (0.8-1 g/kg) 1
• Short course corticosteroids 1
• Single dose anti-D (Rh-positive, non-splenectomized children only) 1

Use IVIg if more rapid platelet increase desired. 1

Contraindications for anti-D in children: Hemoglobin decreased from bleeding or evidence of autoimmune hemolysis. 1

Critical pediatric consideration: Bone marrow examination is unnecessary in children with typical ITP features and is not required before corticosteroid therapy or splenectomy. 1, 4

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Second-Line Treatment (Failed Initial Therapy)

For adults who fail corticosteroids, splenectomy is the most effective single therapy with approximately 50% achieving sustained remission at 5 years. 1, 5

Treatment Algorithm for Corticosteroid Failure:

1. Splenectomy (traditional second-line):

   • Laparoscopic and open approaches offer similar efficacy 1
   • Indicated for patients with persistent/chronic ITP, significant bleeding, lack of response to other therapies 1
   • Delay at least 12 months from diagnosis unless severe bleeding unresponsive to other measures 1
   • Vaccinate before splenectomy (pneumococcal, meningococcal, Haemophilus influenzae type b) 1

2. Thrombopoietin Receptor Agonists (TPO-RAs) - increasingly used before or instead of splenectomy:

   • Romiplostim (Nplate): Starting dose 1 mcg/kg subcutaneous weekly, adjust by 1 mcg/kg increments to achieve platelets ≥ 50 × 10⁹/L, maximum 10 mcg/kg weekly 6
   • Eltrombopag: Alternative oral TPO-RA 7
   • Strongly recommended for patients at bleeding risk who relapse after splenectomy or have contraindication to splenectomy and failed at least one other therapy 1
   • May be considered before splenectomy in patients at bleeding risk who failed one line of therapy 1

3. Rituximab:

   • May be considered for patients at bleeding risk who failed corticosteroids, IVIg, or splenectomy 1
   • Weaker evidence than TPO-RAs or splenectomy 1

Pediatric Second-Line:

For children with significant ongoing bleeding despite IVIg, anti-D, or corticosteroids:

• Rituximab may be considered 1
• High-dose dexamethasone may be considered 1
• Both may be considered as alternatives to splenectomy in chronic ITP 1

Splenectomy in children: Reserved for chronic/persistent ITP with significant bleeding, lack of response to other therapies, or quality of life considerations, but delay at least 12 months unless severe disease. 1

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Third-Line and Refractory ITP

For patients failing splenectomy or multiple therapies, fostamatinib (tyrosine kinase inhibitor) and older immunosuppressives are options. 2, 7

Options include:

• Fostamatinib (FDA-approved tyrosine kinase inhibitor) 7
• Azathioprine, cyclophosphamide, cyclosporine, danazol, dapsone, mycophenolate mofetil 7
• Investigational: Bruton's tyrosine kinase inhibitors, neonatal Fc receptor inhibitors 2

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Special Populations

Pregnancy:

Pregnant patients requiring treatment should receive corticosteroids or IVIg. 1

• Mode of delivery based on obstetric indications, not maternal platelet count 1

HIV-Associated ITP:

Treat the underlying HIV infection with antiretroviral therapy before other ITP-specific treatments unless clinically significant bleeding present. 1

• If ITP treatment required: corticosteroids, IVIg, or anti-D 1
• Splenectomy preferred over other agents for symptomatic patients failing initial therapy 1

Hepatitis C-Associated ITP:

Antiviral therapy should be considered in absence of contraindications, but monitor platelet count closely as interferon may worsen thrombocytopenia. 1

• If ITP treatment required: IVIg is preferred initial treatment 1

Helicobacter pylori-Associated ITP:

Eradication therapy should be administered in patients with documented H. pylori infection (urea breath test, stool antigen, or endoscopic biopsy). 1

• Screening for H. pylori should be considered in ITP patients where eradication would be used if positive 1

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Monitoring and Treatment Goals

Target platelet count is ≥ 50 × 10⁹/L to reduce bleeding risk, not normalization of platelet count. 6, 2

Monitoring schedule:

• During dose adjustment: Weekly complete blood counts 6
• After stable dose established: Monthly complete blood counts 6
• After treatment discontinuation: Weekly for at least 2 weeks 6

Treatment should be discontinued if platelet count does not increase sufficiently to avoid clinically important bleeding after 4 weeks at maximum dose. 6

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Common Pitfalls to Avoid

• Do not treat based on platelet count alone—bleeding severity and risk factors determine treatment need 1, 2
• Do not perform bone marrow examination in typical ITP cases—diagnosis is clinical exclusion 1, 4
• Do not test for antiplatelet antibodies—ITP is a clinical diagnosis, not serologic 4
• Do not rush to splenectomy—defer at least 12 months to allow for spontaneous remission unless severe bleeding 1
• Do not use anti-D in Rh-negative patients, splenectomized patients, or those with anemia from bleeding 1
• Do not aim for complete platelet normalization—goal is safe platelet count (≥ 50 × 10⁹/L) with minimal treatment toxicity 6, 2