What is the primary management approach for a patient with Immune Thrombocytopenic Purpura (ITP)?

Immune Thrombocytopenic Purpura (ITP): Symptoms and Management

Clinical Presentation

ITP presents with isolated thrombocytopenia (platelet count <100 × 10⁹/L) and variable bleeding manifestations ranging from asymptomatic cases to life-threatening hemorrhage. 1

Symptoms

• Many patients are asymptomatic with only incidental thrombocytopenia discovered on routine blood work 1
• Mucocutaneous bleeding including petechiae, purpura, and easy bruising 1
• Epistaxis (nosebleeds) 1
• Gastrointestinal hemorrhage in more severe cases 1
• Intracranial hemorrhage (rare but most serious complication) 1
• The severity of bleeding does not always correlate directly with platelet count; additional factors including age, lifestyle, and comorbidities affect bleeding risk 1

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Primary Management Approach

Treatment Thresholds

Treatment is indicated for platelet counts <30 × 10⁹/L with bleeding symptoms, or <20 × 10⁹/L regardless of symptoms, with the goal of achieving a hemostatic platelet count of 30-50 × 10⁹/L rather than normalization. 2, 3

• No treatment needed if platelet count >50 × 10⁹/L unless patient has active bleeding, requires surgery, has bleeding-predisposing comorbidities, or needs anticoagulation 2
• Hospital admission considered for platelet count <20 × 10⁹/L, especially with significant comorbidities or mucosal bleeding 3
• Outpatient management appropriate for platelet count 20-30 × 10⁹/L if asymptomatic or only minor mucocutaneous bleeding 3

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First-Line Treatment Options

Corticosteroid Therapy (Preferred Initial Approach)

High-dose dexamethasone 40 mg daily for 4 days offers superior initial (up to 90%) and sustained (50-80%) response rates compared to conventional prednisone, with faster response times. 2, 3

Dexamethasone Pulse Regimen

• Dosing: 40 mg/day for 4 days, repeated every 2-4 weeks for 1-4 cycles 2
• Initial response rate: Up to 90% 2, 3
• Sustained response rate: 50-80% with 3-6 cycles 2
• Time to response: Several days to several weeks 2
• One study demonstrated: 86% response rate with 74% having responses lasting median 8 months using 4 cycles given every 14 days 2

Alternative: Conventional Prednisone

• Dosing: 0.5-2 mg/kg/day for 2-4 weeks 2, 3
• Initial response rate: 70-80% 2
• Sustained response: Only 20-40% after discontinuation 2
• Critical limitation: Prolonged courses >6-8 weeks are strongly discouraged due to substantial morbidity including osteoporosis, diabetes, hypertension, avascular necrosis, and opportunistic infections 2
• Tapering strategy: Rapidly taper and discontinue after achieving target platelet count in responders 2

Corticosteroid Side Effects Requiring Monitoring

• Short-term: Mood swings, weight gain, anger, anxiety, insomnia, Cushingoid features, diabetes, fluid retention 2
• Long-term: Osteoporosis, skin changes, hypertension, GI distress, avascular necrosis, immunosuppression, psychosis, cataracts, opportunistic infections 2
• Mandatory monitoring: Hypertension, hyperglycemia, gastric irritation/ulcer formation, myopathy, avascular necrosis, osteoporosis (with prolonged use), quality of life assessment 2

Intravenous Immunoglobulin (IVIg)

IVIg 1 g/kg as a single dose can be combined with corticosteroids for faster platelet response, particularly when rapid increase is required. 1, 3

• Dosing options: 1 g/kg for 1-2 days OR 0.4 g/kg/day for 5 days 1, 2
• Response time: More likely to achieve platelet increase within 24 hours compared to corticosteroids alone 1
• Advantages: Faster response than corticosteroids; useful when corticosteroids contraindicated 2
• Disadvantages: Higher toxicity (especially headaches), prolonged infusion required (several hours), higher cost 1
• Serious toxicities: Renal failure and thrombosis (rare) 1
• Concomitant corticosteroids may: Enhance IVIg response, reduce infusion reactions, prevent aseptic meningitis 1

Anti-D Immunoglobulin

• Dosing: 50-75 μg/kg for Rh(D) positive, non-splenectomized patients 2
• Limited applicability due to requirement for specific patient characteristics 2

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Emergency Management

For uncontrolled bleeding or urgent surgical procedures, combine prednisone and IVIg; consider platelet transfusion (possibly with IVIg), high-dose methylprednisolone, or emergency splenectomy. 1

• Combination therapy recommended: Prednisone + IVIg for emergency treatment 1
• High-dose methylprednisolone may be useful in emergency settings 1
• Platelet transfusion possibly in combination with IVIg 1
• Emergency splenectomy for refractory life-threatening bleeding 1
• Vinca alkaloids show some evidence of rapid response 1
• Plasmapheresis is NOT indicated - no response demonstrated in chronic ITP patients 1

General Supportive Measures

• Cessation of antiplatelet drugs (aspirin, NSAIDs, clopidogrel) unless absolutely necessary 1
• Blood pressure control to minimize bleeding risk 1
• Menstrual suppression in women with heavy menses 1
• Trauma minimization through activity modification 1
• Maintain hemoglobin ≥10 g/dL to improve hemostasis 1
• Desmopressin may improve platelet function 1

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Second-Line Treatment Options

Splenectomy is deferred for at least 6-12 months to allow for spontaneous remission; thrombopoietin receptor agonists (TPO-RAs) and rituximab are preferred medical second-line options. 1, 3

Timing Considerations

• Defer splenectomy for at least 6 months after diagnosis due to possibility of spontaneous improvement or late remission 1
• Some patients may spontaneously remit years after diagnosis 1
• Second-line therapy goals: Attain sustained increase in platelet count to hemostatic level for individual patient with minimal toxicity 1

Thrombopoietin Receptor Agonists (TPO-RAs)

Romiplostim and eltrombopag stimulate platelet production rather than modulating immunity, offering high response rates with continued administration. 1, 4, 5

Romiplostim (Nplate®)

• Dosing: 1-10 μg/kg subcutaneous weekly injection 1
• Response rates: Non-splenectomized 88%, splenectomized 79% 1
• Time to response: 1-4 weeks 1
• FDA-approved indication: Adults and children ≥1 year with ITP who have had insufficient response to corticosteroids, immunoglobulins, or splenectomy 5
• Adverse events (≥20%): Headache, fatigue, epistaxis, arthralgia, contusion (similar to placebo) 1
• Serious adverse events: Increased bone marrow reticulin, worsening thrombocytopenia upon discontinuation, thrombosis 1
• Monitoring required: Weekly platelet counts initially, then monthly once stable dose achieved 5

Eltrombopag (Alvaiz®)

• Dosing: Oral 25,50, or 75 mg daily 1
• Initial dose for ITP: 36 mg once daily for most adults and children ≥6 years 4
• Maximum dose: 54 mg per day for ITP 4
• Dose reductions needed: Hepatic impairment and some East-/Southeast-Asian ancestry patients 4
• Administration requirements: Take without meal or with low-calcium meal (≤50 mg); at least 2 hours before or 4 hours after polyvalent cations (antacids, calcium-rich foods, mineral supplements) 4
• Boxed warnings: Risk of hepatic decompensation in chronic hepatitis C; risk of severe hepatotoxicity requiring liver function monitoring 4

Rituximab

• Dosing: 375 mg/m² weekly × 4 (lower doses may also be effective) 1
• Response rate: 60% overall; 40% complete response 1
• Time to response: 1-8 weeks 1
• Sustained response: Approximately two-thirds of responders maintain response without additional therapy over 5-10 years 1
• Mechanism: Intended to induce long-term remission (given as single course) 1
• Adverse events: Usually mild-to-moderate first-infusion reactions (fever/chills, rash, throat scratchiness); more severe reactions include serum sickness and rarely bronchospasm, anaphylaxis 1

Splenectomy

• Response: Approximately two-thirds achieve normal platelet counts initially 6, 7
• Long-term outcomes: Nearly 50% experience recurrent thrombocytopenia by 5 years post-splenectomy 7
• Consideration: Permanent surgical procedure with potentially life-threatening infectious sequelae 6
• Timing: Generally delayed for at least 12 months unless severe disease 3

Other Immunosuppressive Agents

Azathioprine

• Dosing: 1-2 mg/kg (maximum 150 mg/day) 1
• Response rate: Up to two-thirds; 40-45% complete response 1
• Time to response: Slow; may need 3-6 months 1
• Duration: Continued therapy generally required, often at reduced dose 1
• Toxicities: Generally mild - weakness, sweating, transaminase elevations, severe neutropenia with infection, pancreatitis 1

Cyclosporin A

• Dosing: 2.5-3 mg/kg/day (titration to blood levels 100-200 ng/mL) 1
• Response rate: >80% clinical improvement; 42-50% complete response 1
• Time to response: 3-4 weeks 1
• Sustained response: Durable remissions (mean 29 months) following discontinuation 1
• Toxicities: Moderate but transient - increased creatinine, hypertension, fatigue, paresthesias, gingival hyperplasia, myalgia, dyspepsia, hypertrichosis, tremor 1
• Unsuitable for: Older patients and those with renal insufficiency 1

Cyclophosphamide

• Dosing: Oral 1-2 mg/kg daily for ≥16 weeks OR IV 0.3-1 g/m² for 1-3 doses every 2-4 weeks 1
• Response rate: 24-85% 1
• Time to response: 1-16 weeks 1
• Toxicities: Mild to moderate - neutropenia, deep venous thrombosis, nausea, vomiting 1
• Serious concerns: Reports of acute myeloid leukemia in ITP/SLE patients; sterility not adequately addressed 1

Dapsone

• Dosing: 75-100 mg daily 1
• Response rate: Up to 50% 1
• Time to response: 3 weeks 1
• Mechanism: Moderate corticosteroid-sparing agent 1
• May delay splenectomy: Up to 32 months in responders 1
• Toxicities: Infrequent and reversible - abdominal distension, anorexia, nausea, methemoglobinuria; hemolytic anemia in G6PD deficiency; severe skin rash may require discontinuation 1

Mycophenolate Mofetil

• Dosing: 1000 mg twice daily for ≥3-4 weeks 1
• Response rate: Up to 75%; complete response up to 45% 1
• Time to response: 4-6 weeks 1
• Toxicities: Mild and infrequent - headache (most common and dose-limiting), backache, abdominal distension, anorexia, nausea 1

Danazol

• Dosing: 200 mg 2-4 times daily 1
• Response rate: 67% complete or partial response; 40% in anecdotal reports 1
• Time to response: 3-6 months 1
• Sustained response: 46% remained in remission at median 119 months 1
• Toxicities: Frequent - acne, increased facial hair, increased cholesterol, amenorrhea, transaminitis 1

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Monitoring and Follow-up

Ensure hematology follow-up within 24-72 hours of diagnosis; monitor platelet counts weekly during dose adjustment, then monthly once stable. 3, 5

• Initial monitoring: Weekly platelet counts and dose adjustments until stable 3, 5
• Maintenance monitoring: Monthly platelet counts once dose stabilized 5
• After discontinuation: Platelet counts for at least 2 weeks to check for rebound thrombocytopenia 5
• Assess for: Corticosteroid side effects, health-related quality of life, bleeding symptoms 3
• Report any bruising or bleeding during treatment 5

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Common Pitfalls and Caveats

• Avoid prolonged corticosteroid courses (>6-8 weeks) due to significant morbidity 2
• Do not aim for normal platelet counts - target is hemostatic level (30-50 × 10⁹/L) to minimize treatment toxicity 2, 3
• Eltrombopag absorption significantly reduced by polyvalent cations - strict timing requirements for administration 4
• TPO-RA discontinuation may cause rebound severe thrombocytopenia - requires careful monitoring 1, 5
• Bone marrow examination not routinely needed in patients with typical ITP presentation 3
• Screen for HCV and HIV in all newly diagnosed ITP patients 3
• Increased thrombosis risk with TPO-RAs, particularly if platelet count becomes excessively elevated 1, 5
• Hepatotoxicity monitoring mandatory with eltrombopag 4