What are the treatment options for autoimmune causes of thrombocytopenia, such as Immune Thrombocytopenic Purpura (ITP)?

Treatment of Autoimmune Thrombocytopenia (ITP)

When to Initiate Treatment

Treatment should be initiated when platelet count is <30 × 10⁹/L with bleeding risk, not to normalize platelet counts—the target is 30-50 × 10⁹/L to reduce bleeding risk. 1

• Treatment is rarely needed if platelet count >50 × 10⁹/L unless active bleeding, planned surgery, bleeding-predisposing comorbidities, or anticoagulation requirement exists 1
• Treatment decisions should prioritize bleeding severity, bleeding risk, activity level, and quality of life over platelet count alone 2
• Screen for secondary causes including H. pylori, HIV, HCV, antiphospholipid syndrome, and lymphoproliferative disorders before initiating therapy 1

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First-Line Treatment Options

Corticosteroids (Standard Approach)

Prednisone 0.5-2 mg/kg/day remains the most commonly recommended first-line therapy, producing initial response in 70-80% of patients but sustained responses in only 20-40%. 3, 2

• Rapidly taper and discontinue prednisone after achieving target platelet count to minimize toxicity 3
• Prolonged corticosteroid use (>6-8 weeks) should be avoided due to significant side effects including weight gain, mood alterations, hypertension, diabetes, osteoporosis, and increased infection risk 2

High-Dose Dexamethasone (Preferred for Severe Cases)

High-dose dexamethasone 40 mg/day for 4 days offers superior response rates (up to 90% initial, 50-80% sustained) compared to conventional prednisone and works faster. 3, 1

• Dexamethasone can be repeated every 2-4 weeks for 1-4 cycles if needed 3
• Time to response ranges from several days to several weeks 3
• One study demonstrated 4 cycles given every 14 days produced 86% response rate with 74% having responses lasting a median of 8 months 3
• Dexamethasone appears safer with lower incidence of adverse events compared to prednisone, likely reflecting shorter treatment duration 4

Intravenous Immunoglobulin (IVIg)

IVIg 1 g/kg as a single dose should be used with corticosteroids when rapid platelet increase is required (within 24 hours), or as monotherapy if corticosteroids are contraindicated. 1

• IVIg recipients are more likely to attain platelet increase within 24 hours compared to corticosteroids 5
• Alternative dosing: 0.4 g/kg/day for 5 days 3
• Common toxicities include headaches requiring prolonged infusion (over several hours); rare but serious toxicities include renal failure and thrombosis 5
• Concomitant corticosteroids may enhance IVIg response and reduce infusion reactions 5

Anti-D Immunoglobulin

• Anti-D 50-75 μg/kg can be used for Rh(D) positive, non-splenectomized patients as alternative first-line option 3, 1
• Should not be used in children with decreased hemoglobin from bleeding or evidence of autoimmune hemolysis 5

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Emergency Treatment for Active Bleeding

For patients with uncontrolled bleeding or CNS/GI/genitourinary hemorrhage, combine prednisone and IVIg immediately. 5

• High-dose methylprednisolone (HDMP) may also be useful in emergency settings 5
• Platelet transfusion, possibly in combination with IVIg, provides rapid response 5
• Emergency splenectomy is an option for life-threatening bleeding 5
• Vinca alkaloids show evidence of rapid response 5
• General measures: cease antiplatelet drugs, control blood pressure, inhibit menses, minimize trauma 5

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Second-Line Treatment for Steroid-Refractory ITP

Thrombopoietin Receptor Agonists (TPO-RAs) - Preferred

TPO-RAs (romiplostim, eltrombopag) are the preferred second-line therapy for long-term management, with overall platelet response rates of 88% in non-splenectomized and 79% in splenectomized patients. 2

• Romiplostim: Start 1 mcg/kg subcutaneously weekly, adjust by 1 mcg/kg increments to achieve platelet count ≥50 × 10⁹/L, maximum 10 mcg/kg weekly 6
• Median effective dose in adults: 2-3 mcg/kg weekly 6
• Sustained responses documented for up to 4 years with continuous administration 2
• Up to 30% of patients may achieve remission after tapering and discontinuation 2
• Monitor for bone marrow reticulin formation during therapy 1
• Patients not responding to one TPO-RA may respond to the alternate agent 2

Splenectomy

Splenectomy offers 80% initial response rate and 66% sustained response for at least 5 years, making it an excellent option for patients who have failed corticosteroid therapy. 1

• Historically the gold standard second-line therapy 2
• Should be considered for patients at risk of bleeding who relapse after other therapies 1
• Given efficacy of medical therapies and rate of spontaneous remission in first year, splenectomy is frequently deferred in modern algorithms 7

Rituximab

Rituximab 375 mg/m² weekly for 4 weeks achieves responses in 60% of patients with complete responses in 40%. 5, 2

• Response typically occurs within 1-8 weeks of treatment initiation 2
• Long-term responses documented in 20-30% of cases 2
• Common side effects include first-infusion fever/chills, rash, throat scratchiness; more severe reactions can occur 5

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Third-Line Treatment Options

For patients failing TPO-RAs, splenectomy, and rituximab, consider the following agents:

• Azathioprine 1-2 mg/kg daily: Response in up to two-thirds of patients, but requires 3-6 months for effect 5, 2
• Cyclosporin A 5 mg/kg/day initially, then 2.5-3 mg/kg/day: Response rates 50-80% within 3-4 weeks 5, 2
• Cyclophosphamide 1-2 mg/kg orally daily or 0.3-1 g/m² IV every 2-4 weeks: Response in 24-85% of patients 5, 2
• Danazol 200 mg 2-4 times daily: Response in up to 67% of patients but requires 3-6 months 5, 2
• Dapsone 75-100 mg daily: Response in up to 50% of patients within 3 weeks 5, 2
• Mycophenolate mofetil 1000 mg twice daily: Response in up to 75% of patients within 4-6 weeks 5, 2

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Special Populations

Pregnant Patients

Pregnant patients requiring treatment should receive either corticosteroids or IVIg only. 1

HIV-Associated ITP

Treat HIV infection with antiviral therapy before other ITP treatments unless clinically significant bleeding complications exist. 1

HCV-Associated ITP

• Consider antiviral therapy in absence of contraindications, but monitor platelet count closely as interferon may worsen thrombocytopenia 1
• If ITP treatment required, use IVIg as initial therapy 1

H. Pylori-Associated ITP

Administer eradication therapy in patients with confirmed H. pylori infection (based on urea breath test, stool antigen, or endoscopic biopsy). 1

CLL-Associated Autoimmune Cytopenia

• First treatment option is corticosteroids 5
• Autoimmune cytopenias not responding to conventional therapy are indications for CLL treatment 5
• Rituximab or splenectomy are options for refractory cases; thrombopoietin analogs have shown effectiveness in ITP-related CLL not responding to corticosteroids 5

Patients on Antiplatelet Therapy

Target higher platelet threshold (>50 × 10⁹/L) to compensate for increased bleeding risk. 1

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Critical Pitfalls to Avoid

• Do not attempt to normalize platelet counts—this increases treatment toxicity without improving outcomes 6
• Avoid prolonged corticosteroid therapy beyond 6-8 weeks—patients requiring on-demand corticosteroids after first-line treatment should be considered non-responders and promptly switched to second-line therapy 2
• Do not abruptly interrupt TPO-RAs or make excessive dose adjustments—this causes platelet fluctuations, especially in splenectomized patients 2
• Discontinue TPO-RAs if platelet count does not increase sufficiently after 4 weeks at maximum dose (10 mcg/kg) 6
• Monitor CBC weekly for at least 2 weeks following TPO-RA discontinuation 6