What are the diagnostic criteria and treatment guidelines for Immune Thrombocytopenic Purpura (ITP)?

Diagnostic Criteria for Immune Thrombocytopenic Purpura (ITP)

ITP is defined by a peripheral blood platelet count less than 100 × 10⁹/L in the absence of any obvious initiating or underlying cause of thrombocytopenia. 1

Essential Diagnostic Workup

The diagnosis relies on exclusion of other causes through a focused evaluation 2:

Required Initial Tests

• Complete blood count (CBC) with platelet count - the fundamental first test 3
• Peripheral blood smear examination - must show specific findings 2, 1:
  • Thrombocytopenia with normal-sized or slightly larger platelets (not giant platelets approaching RBC size)
  • Normal red blood cell morphology (no schistocytes or poikilocytosis unless from bleeding response)
  • Normal white blood cell morphology (though atypical lymphocytes and eosinophilia may occur in children)
• Patient history and physical examination - looking specifically for 1:
  • Duration and pattern of bleeding symptoms
  • Family history of bleeding disorders
  • Medication exposure
  • Recent viral infections (especially in children)
  • Absence of splenomegaly (may be palpable in 12% of children but should raise concern in adults) 2

Conditional Testing Based on Risk Factors

• HIV and HCV antibody testing - required in patients with risk factors 2, 1
• Abdominal CT scan or ultrasound - only if splenomegaly is suspected on physical examination 2, 3
• Pregnancy-specific tests - blood pressure and liver function tests to exclude preeclampsia 3

When Bone Marrow Examination Is Indicated

Bone marrow aspiration should be performed in 2, 1:

• Patients with persistent thrombocytopenia lasting more than 6-12 months
• Patients unresponsive to initial therapy (IVIg or corticosteroids)
• Patients with atypical presenting features

Bone marrow examination should NOT be performed routinely before initiating IVIg therapy or in typical presentations 2, 1

Tests That Are NOT Routinely Indicated

The following tests have uncertain appropriateness and should not be performed routinely 2:

• ANA (antinuclear antibody)
• Direct antiglobulin test
• Platelet antigen-specific antibody
• Platelet-associated IgG
• Mean platelet volume
• Serum immunoglobulins
• Lupus anticoagulant/antiphospholipid antibodies

Disease Classification by Duration

ITP is classified into three temporal categories 1:

• Newly diagnosed: < 3 months duration
• Persistent: 3-12 months duration
• Chronic: ≥ 12 months duration

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Treatment Guidelines for ITP

Initial Management Decisions

Adults with Newly Diagnosed ITP

Treatment thresholds are based on platelet count and bleeding symptoms, not platelet count alone 2, 1:

• Platelet count ≥30 × 10⁹/L with no/minimal bleeding: Observation without treatment 1
• Platelet count 20-30 × 10⁹/L: Outpatient management if asymptomatic or minor mucocutaneous bleeding only 2
• Platelet count <20 × 10⁹/L: Consider hospitalization if significant mucous membrane bleeding present 2
• Platelet count <10 × 10⁹/L: Treatment indicated even with minor purpura 2, 1

Hospitalization is required for 2:

• Patients refractory to treatment
• Significant comorbidities with bleeding risk
• Social concerns or uncertainty about diagnosis
• More significant mucosal bleeding

Children with Newly Diagnosed ITP

Children with platelet counts >30 × 10⁹/L should not be hospitalized and do not routinely require treatment if asymptomatic or have only minor purpura 2

Treatment is indicated for children with 2:

• Platelet counts <20 × 10⁹/L AND significant mucous membrane bleeding
• Platelet counts <10 × 10⁹/L AND minor purpura

First-Line Treatment Options

For Adults

Corticosteroids are the standard initial treatment 1:

• Short course (≤6 weeks including taper) is strongly recommended over prolonged courses (>6 weeks) 2
• Specific regimens vary but shorter is better to minimize side effects 2

The ASH guideline panel suggests corticosteroids alone rather than rituximab plus corticosteroids for initial therapy 2, though patients who highly value remission possibility over rituximab side effects may prefer combination therapy

Intravenous immunoglobulin (IVIg) 1:

• Used when rapid platelet count increase is required
• Initial dose: 1 g/kg as one-time dose, repeatable if necessary
• Appropriate for third trimester pregnant women with platelet counts <10 × 10⁹/L 1

Anti-D immunoglobulin 1:

• Alternative first-line option if corticosteroids are contraindicated
• Only effective in Rh-positive, non-splenectomized patients

For Children

Observation is preferred over treatment for children with no or minor bleeding 2

When treatment is required (non-life-threatening mucosal bleeding and/or diminished quality of life), options include 2:

• Corticosteroids (prednisone 2-4 mg/kg/day for 5-7 days, maximum 120 mg daily, OR dexamethasone 0.6 mg/kg/day, maximum 40 mg/day × 4 days)
• IVIg
• Anti-D immunoglobulin

Corticosteroid courses longer than 7 days should be avoided in children 2

Life-Threatening Bleeding

For severe, life-threatening bleeding, immediate hospitalization with 2, 1:

• High-dose parenteral glucocorticoid therapy
• IVIg
• Platelet transfusions
• Conventional critical care measures

Second-Line Treatment (ITP ≥3 Months, Corticosteroid-Dependent or Unresponsive)

Treatment Options and Hierarchy

Three main second-line options exist, with conditional recommendations based on patient values 2:

1. Splenectomy 2, 1:

   • Most effective treatment with two-thirds achieving durable complete remissions 4
   • Should be delayed at least 1 year after diagnosis due to potential for spontaneous remission 2
   • Requires appropriate preoperative immunizations and counseling 2
   • Preferred by patients who value avoiding long-term medication 2

2. Thrombopoietin receptor agonists (TPO-RAs) 2, 1:

   • Either eltrombopag (oral daily) or romiplostim (subcutaneous weekly) are suggested 2
   • Choice depends on patient preference for oral vs. subcutaneous administration 2
   • Preferred by patients who wish to avoid surgery 2
   • Recommended for patients who relapse after splenectomy or have contraindications to splenectomy 1

3. Rituximab 2, 1:

   • May be considered for patients at risk of bleeding who have failed first-line therapy 1
   • Preferred by patients who value avoiding long-term medication and surgery 2

Comparative Recommendations

The ASH guideline panel suggests 2:

• TPO-RA rather than rituximab (conditional recommendation)
• Rituximab rather than splenectomy (conditional recommendation)
• Either splenectomy or TPO-RA (conditional recommendation - equipoise)

The choice should be individualized based on 2:

• Duration of ITP
• Frequency of bleeding episodes requiring hospitalization or rescue medication
• Comorbidities and age
• Medication adherence capability
• Medical and social support networks
• Patient values regarding surgery, long-term medication, and durability of response
• Cost and availability

Special Populations

Pregnant Women

Treatment thresholds differ in pregnancy 1:

• Platelet counts >50 × 10⁹/L: No routine treatment required
• Platelet counts <10 × 10⁹/L: Treatment required
• Platelet counts 10-30 × 10⁹/L in second or third trimester with bleeding: Treatment required
• IVIg is appropriate initial treatment for third trimester patients with platelet counts <10 × 10⁹/L 1

Critical Pitfalls and Caveats

There is no "gold standard" test that can reliably establish the diagnosis of ITP 1 - diagnosis remains one of exclusion

Response to ITP-specific therapy supports but does not confirm the diagnosis and does not exclude secondary ITP 1

Platelet transfusions should be reserved for severe, life-threatening bleeding only 2, 1 - they are not indicated for prophylaxis in stable patients

The goal of treatment is to achieve a platelet count associated with adequate hemostasis, NOT a normal platelet count 5, 6

Immature platelet fraction (IPF) is typically elevated in ITP but rare cases with low IPF exist, which may necessitate bone marrow biopsy to exclude bone marrow failure 7

All current treatments carry risks - the frequency of death from treatment complications is similar to the frequency of death from bleeding in ITP 4

Follow-up with a hematologist should occur within 24-72 hours of diagnosis or disease relapse 2