At what platelet count or bleeding severity should treatment for immune thrombocytopenia be initiated, and what are the recommended first‑line and second‑line therapies for adults, children, and pregnant patients?

Management of Immune Thrombocytopenia (ITP)

Treatment Initiation Thresholds

Treatment should be initiated in adults with newly diagnosed ITP when the platelet count is <30 × 10⁹/L, particularly if mucosal bleeding (epistaxis, gingival bleeding, menorrhagia) is present or high-risk bleeding factors exist (hypertension, need for anticoagulation, age >60 years). 1, 2

• Observation without treatment is appropriate when platelet count is >30 × 10⁹/L with only skin manifestations (petechiae, bruising) and no bleeding risk factors. 2
• For platelet counts between 20-30 × 10⁹/L, treatment decisions depend on bleeding severity, comorbidities, and activity level. 2
• Severe bleeding is distinctly uncommon when platelet count is >30 × 10⁹/L and usually only occurs when counts fall <10 × 10⁹/L. 3
• The goal is to elevate platelet counts to a safety level (>20-30 × 10⁹/L) rather than normalize counts, while minimizing treatment toxicity. 4

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First-Line Therapy for Adults

Corticosteroids (Preferred Initial Treatment)

Longer courses of corticosteroids are preferred over shorter courses or IVIG alone as first-line treatment. 1

Prednisone 1 mg/kg orally daily for 21 days followed by a taper (total ≤6 weeks) is the preferred first-line corticosteroid regimen, yielding longer duration of response than short-course dexamethasone. 2, 5

• Prednisone should be rapidly tapered in responders and stopped after 4 weeks in non-responders to limit corticosteroid toxicity. 5
• Avoid corticosteroid courses longer than 6 weeks because additional toxicity is not offset by increased efficacy. 2
• Initial corticosteroid response occurs in 70-80% of patients, though sustained responses are only seen in 20-40%. 6

High-dose dexamethasone 40 mg orally daily for 4 days provides rapid platelet rise (initial response up to 90%) and is useful when swift increase is needed or when minimizing prolonged steroid exposure. 2, 5

• Dexamethasone yields sustained remission in 50-80% of patients when given as 1-4 cycles every 2-4 weeks. 5

Adding IVIG to Corticosteroids

IVIG 1 g/kg as a single dose should be added to corticosteroids when a more rapid platelet increase is required (e.g., active bleeding, urgent surgery). 1, 6, 5

• IVIG achieves platelet response within 2-4 days, faster than standard prednisone (8.4 days) but similar to high-dose methylprednisolone (4.7 days). 6
• Response typically occurs within 24 hours in emergency bleeding situations. 6, 5
• IVIG produces responses in up to 80% of patients. 5
• The dose may be repeated if necessary. 1

Alternative First-Line Options

Either IVIG or anti-D immunoglobulin (in appropriate patients) should be used as first-line treatment if corticosteroids are contraindicated. 1, 5

• Anti-D 50-75 µg/kg is an option for Rh-positive, non-splenectomized patients with initial response rates comparable to IVIG. 5
• Anti-D therapy is contraindicated in children or adults with hemoglobin decreased due to bleeding or with evidence of autoimmune hemolysis. 1, 5
• IVIG may be particularly appropriate as first-line therapy for patients with suboptimal diabetes control, as corticosteroids will significantly worsen glycemic control. 6

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Second-Line Therapy for Adults (≥3 Months Duration)

Thrombopoietin Receptor Agonists (TPO-RAs) - Preferred Second-Line

Thrombopoietin receptor agonists (TPO-RAs) are the preferred second-line therapy for patients who are corticosteroid-dependent or refractory, superseding rituximab and splenectomy. 2

• TPO-RAs 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, 5
• Either eltrombopag (oral daily) or romiplostim (subcutaneous weekly) may be chosen based on patient preference; both have comparable efficacy. 1, 2
• TPO-RAs achieve platelet responses in 70-80% of treated patients. 5
• Advantages include avoidance of surgery, reversibility of effect, and proven efficacy in bleeding prevention. 2
• TPO-RAs may be considered for patients at risk of bleeding who have failed one line of therapy (corticosteroids or IVIG) and have not had splenectomy. 1

Splenectomy

Splenectomy is recommended for patients who have failed corticosteroid therapy and is the definitive surgical option for those who accept operative intervention. 1, 5

• Splenectomy should be delayed for at least 12 months from diagnosis unless the disease is severe, unresponsive, or quality-of-life considerations dictate earlier intervention. 2, 5
• Splenectomy provides 80-85% initial response rate with 60-66% sustained long-term responses. 5
• Both laparoscopic and open splenectomy offer similar efficacy. 1, 5
• Up to 30% of initial responders relapse, typically within the first 2 years post-splenectomy. 5

Critical splenectomy preparation and risks:

• Administer polyvalent pneumococcal, meningococcal C conjugate, and Haemophilus influenzae b vaccines at least 4 weeks before surgery. 5
• Patients experience 3-fold increased risk of septicemia, 4.5-fold increased risk of pulmonary embolism, and 2.7-fold increased risk of venous thromboembolism persisting >10 years. 5
• Lifelong prophylactic antibiotics are required (phenoxymethylpenicillin 250-500 mg orally twice daily, or erythromycin 250-500 mg twice daily if penicillin-allergic). 5
• Patients should keep home supply of amoxicillin (3 g loading dose followed by 1 g every 8 hours) for immediate use at first sign of fever. 5

Rituximab

Rituximab may be considered for patients at risk of bleeding who have failed one line of therapy (corticosteroids, IVIG, or splenectomy). 1, 5

• Rituximab is preferred over splenectomy for patients who wish to avoid surgery or have contraindications to operative intervention; however, TPO-RA therapy is still favored when directly comparing rituximab to TPO-RA. 2
• Use of rituximab can allow further delay of splenectomy while pursuing medical management. 5

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First-Line Therapy for Children

Observation vs. Treatment

Children with no bleeding or mild bleeding (skin manifestations only such as bruising and petechiae) should be managed with observation alone regardless of platelet count. 1

• The decision to treat relies on frequency and severity of bleeding and impact on quality of life. 1

When Treatment is Required

For pediatric patients requiring treatment, a single dose of IVIG (0.8-1 g/kg) or a short course of corticosteroids should be used as first-line treatment. 1

IVIG can be used if a more rapid increase in platelet count is desired. 1

• IVIG is generally preferred at a dose of 0.8-1.0 g/kg, with children receiving corticosteroids being 26% less likely to achieve platelet count >20 × 10⁹/L at 48 hours compared to IVIG. 1

A single dose of anti-D can be used as first-line treatment in Rh-positive, non-splenectomized children requiring treatment. 1

• Anti-D therapy is not advised in children with hemoglobin decreased due to bleeding or with evidence of autoimmune hemolysis. 1

If corticosteroids are chosen, there is no evidence to support any one dose or dosing regimen over others; long-term corticosteroids should be avoided in children with acute ITP because of side effects. 1

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Second-Line Therapy for Children

Rituximab may be considered for children or adolescents with ITP who have significant ongoing bleeding despite treatment with IVIG, anti-D, or conventional doses of corticosteroids. 1

• Rituximab may also be considered as an alternative to splenectomy in children with chronic ITP or in patients who do not respond favorably to splenectomy. 1

High-dose dexamethasone may be considered for children or adolescents with significant ongoing bleeding despite first-line treatments. 1

• High-dose dexamethasone may also be considered as an alternative to splenectomy in children with chronic ITP. 1

Splenectomy is recommended for children and adolescents with chronic or persistent ITP who have significant or persistent bleeding, lack of responsiveness or intolerance to other therapies (corticosteroids, IVIG, anti-D), and/or who have need for improved quality of life. 1, 5

• Splenectomy or other interventions with potentially serious complications should be delayed for at least 12 months unless accompanied by severe disease unresponsive to other measures or quality-of-life considerations. 1, 5

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Management During Pregnancy

Pregnant patients requiring treatment should receive either corticosteroids or IVIG. 1, 5

For pregnant women with ITP, the mode of delivery should be based on obstetric indications, not maternal platelet count. 1, 5

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Special Situations: Secondary ITP

HCV-Associated ITP

In patients with secondary ITP due to HCV infection, antiviral therapy should be considered in the absence of contraindications, though platelet count should be closely monitored due to risk of worsening thrombocytopenia from interferon. 1

• If treatment for ITP is required, initial treatment should be IVIG. 1

HIV-Associated ITP

For patients with secondary ITP due to HIV, treatment of HIV infection with antiviral therapy should be considered before other treatment options unless the patient has clinically significant bleeding complications. 1

• If treatment for ITP is required, initial treatment should consist of corticosteroids, IVIG, or anti-D. 1
• Splenectomy is preferred over other agents in symptomatic patients who fail corticosteroids, IVIG, or anti-D. 1

H. pylori-Associated ITP

Eradication therapy should be administered in patients who are found to have H. pylori infection (based on urea breath tests, stool antigen tests, or endoscopic biopsies). 1

• Screening for H. pylori should be considered in patients with ITP in whom eradication therapy would be used if testing is positive. 1

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Post-Treatment Monitoring

Do not treat asymptomatic patients after splenectomy who have platelet counts >30 × 10⁹/L. 1, 5

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Critical Pitfalls to Avoid

• Do not perform bone marrow examination in patients with typical ITP (isolated thrombocytopenia with normal/increased megakaryocytes), as it is unnecessary regardless of age. 1, 2
• Do not continue prednisone beyond 4 weeks in non-responders to minimize corticosteroid toxicity. 5
• Do not use anti-D immunoglobulin when TTP is a diagnostic consideration; anti-D is indicated only for ITP. 2
• Do not assume phenoxymethylpenicillin prophylaxis covers Haemophilus influenzae after splenectomy; vaccination remains essential. 5
• Do not delay emergency-department evaluation after initiating home antibiotics for fever in splenectomy patients, as clinical deterioration can be rapid. 5