What are the diagnostic criteria and treatment options for immune thrombocytopenic purpura (ITP)?

Diagnostic Criteria and Treatment Options for Immune Thrombocytopenic Purpura (ITP)

The diagnosis of ITP is based principally on the history, physical examination, complete blood count, and examination of the peripheral blood smear, which should exclude other causes of thrombocytopenia. 1

Diagnostic Criteria

Definition and Basic Criteria

• ITP is defined as a peripheral blood platelet count less than 100 × 10^9/L with the absence of any obvious initiating or underlying cause 1
• ITP is classified by duration into:
  • Newly diagnosed (< 3 months)
  • Persistent (3-12 months)
  • Chronic (≥ 12 months) 1

Essential Diagnostic Workup

• Basic evaluation (required):
  • Patient history (to exclude drug-induced thrombocytopenia, systemic diseases, infections) 1
  • Family history (to exclude inherited thrombocytopenia) 1
  • Physical examination (should be normal except for bleeding manifestations; significant splenomegaly suggests alternative diagnosis) 1
  • Complete blood count and reticulocyte count (isolated thrombocytopenia with otherwise normal CBC) 1
  • Peripheral blood film examination (normal red and white cell morphology) 1
  • HIV and HCV testing 1

Peripheral Blood Smear Findings

• Consistent with ITP:
  • Thrombocytopenia with normal or slightly larger platelets
  • Normal red blood cell morphology
  • Normal white blood cell morphology 1
• Not consistent with ITP:
  • Red blood cell poikilocytosis, schistocytes, or giant platelets
  • Abnormal white cell morphology 1

Additional Testing

• Bone marrow examination:
  • Not necessary in patients presenting with typical ITP 1
  • Should be performed in patients with persistent thrombocytopenia (>6-12 months) 1
  • Indicated in patients unresponsive to initial therapy 1
  • Recommended for patients with atypical features suggesting other diagnoses 1
• Tests of potential utility in specific situations:
  • Glycoprotein-specific antibody
  • Antiphospholipid antibodies
  • Antithyroid antibodies and thyroid function
  • Antinuclear antibodies
  • H. pylori testing 1

Treatment Options

Treatment Indications

• Treatment decisions should be based on bleeding risk rather than platelet count alone 2
• Treatment is generally indicated for:
  • Adults with platelet counts <30 × 10^9/L 1
  • Patients with platelet counts <20-30 × 10^9/L due to significantly greater bleeding risk 2
  • Patients with platelet counts <50 × 10^9/L with significant mucous membrane bleeding 2

First-Line Treatment for Adults

• Corticosteroids are the standard initial treatment 3, 2
  • Longer courses preferred over shorter courses 1
• Intravenous immunoglobulin (IVIg):
  • Used when rapid increase in platelet count is required 1
  • Initial dose should be 1 g/kg as a one-time dose, repeatable if necessary 1
  • First-line option if corticosteroids are contraindicated 1
• Anti-D immunoglobulin (in Rh-positive, non-splenectomized patients):
  • Alternative first-line option if corticosteroids are contraindicated 1

Second-Line Treatment

• Splenectomy:
  • Recommended for patients who have failed corticosteroid therapy 1
  • Can produce long-lasting response in majority of patients 2
  • Consider delaying for at least 12 months in children and adolescents unless severe disease is present 1
• Rituximab:
  • May be considered for patients at risk of bleeding who have failed first-line therapy or splenectomy 1
• Thrombopoietin receptor agonists (TPO-RAs):
  • Recommended for patients who relapse after splenectomy or have contraindications to splenectomy 1
  • May be considered for patients who have failed one line of therapy before splenectomy 1, 4

Treatment for Refractory ITP

• Options for patients with persistent severe thrombocytopenia despite first- and second-line treatments include:
  • Combination therapies 5
  • Fostamatinib 3
  • Immunosuppressive agents 5
  • Clinical trials of emerging therapies 5

Special Populations: Pregnant Women

• Pregnant women with ITP and platelet counts >50,000 do not routinely require treatment 1
• Treatment is required for pregnant women with:
  • Platelet counts <10,000 1
  • Platelet counts 10,000-30,000 in second or third trimester with bleeding 1
• IVIg is appropriate initial treatment for women with platelet counts <10,000 in the third trimester 1

Common Pitfalls and Caveats

• There is no "gold standard" test that can reliably establish the diagnosis of ITP 1, 6
• Response to ITP-specific therapy is supportive of diagnosis but does not exclude secondary ITP 1
• Mild splenomegaly may be found in younger patients, but moderate or massive splenomegaly suggests an alternative cause 1
• Constitutional symptoms such as fever, weight loss, hepatomegaly, or lymphadenopathy suggest underlying disorders like HIV, SLE, or lymphoproliferative disease 1
• The immature platelet fraction (IPF) is typically elevated in ITP but can be low in some cases, complicating diagnosis 6
• Bone marrow examination should not be performed routinely before initiating IVIg therapy 1
• Platelet transfusions should be reserved for patients with severe, life-threatening bleeding 1