What are the diagnostic steps and treatment options for Immune Thrombocytopenic Purpura (ITP)?

Diagnosis of Immune Thrombocytopenic Purpura (ITP)

ITP is diagnosed when the platelet count falls below 100 × 10⁹/L without any identifiable underlying cause, confirmed through a systematic exclusion of alternative diagnoses. 1

Diagnostic Criteria

The diagnosis requires isolated thrombocytopenia without anemia or leukopenia, with a peripheral smear showing normal or slightly larger platelets and no schistocytes. 2 ITP remains fundamentally a diagnosis of exclusion—there is no gold standard confirmatory test. 1, 3

Essential Initial Workup

The basic evaluation must include: 1

• Complete blood count with differential to confirm isolated thrombocytopenia versus pancytopenia 2, 4
• Peripheral blood smear examination to exclude pseudothrombocytopenia (EDTA-dependent platelet clumping) and identify abnormal cell morphology 1, 2, 4
• Patient and family history to identify inherited thrombocytopenias or secondary causes 1
• Physical examination that should be normal except for bleeding manifestations 1

Red Flags Requiring Additional Investigation

The presence of splenomegaly, hepatomegaly, or lymphadenopathy strongly suggests secondary causes of thrombocytopenia rather than primary ITP. 2, 4 Other concerning features include: 4

• Non-petechial rash
• Abnormal hemoglobin or white blood cell count
• Abnormal white cell morphology
• Constitutional symptoms (fever, weight loss, bone pain)

Mandatory Infectious Disease Screening

HIV and hepatitis C testing are recommended as part of the standard diagnostic workup in adults. 1, 2 H. pylori testing should also be considered, as eradication therapy can improve platelet counts in H. pylori-associated ITP. 4

When Bone Marrow Examination Is Required

Bone marrow examination is NOT necessary in patients presenting with typical ITP features. 1, 2 However, it becomes mandatory in specific circumstances: 1, 4

• Age ≥60 years (to exclude myelodysplastic syndromes, leukemias, or other malignancies)
• Persistent thrombocytopenia or atypical features (abnormalities beyond isolated thrombocytopenia)
• Systemic symptoms present (fever, weight loss, bone pain)
• Before splenectomy consideration
• Minimal or no response to first-line ITP therapies

Critical Caveat About Immature Platelet Fraction (IPF)

While elevated IPF typically supports ITP diagnosis by demonstrating increased platelet production, severe ITP can paradoxically present with low IPF, necessitating bone marrow examination to exclude bone marrow failure. 3 Do not assume elevated IPF definitively confirms ITP, and never rely solely on IPF in patients over 60 years. 4

Disease Classification by Duration

ITP is categorized as: 1

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

Treatment Thresholds

Adults

Treatment is recommended for adults with platelet counts <30 × 10⁹/L. 1, 2 However, treatment decisions should prioritize bleeding symptoms over platelet count alone. 2, 5 Bleeding risk increases significantly when platelet counts fall below 10-20 × 10⁹/L. 5

Children

For children with platelet counts >30 × 10⁹/L and no bleeding or only minor purpura, observation alone is recommended regardless of platelet count. 2, 4 Treatment is indicated for children with: 2

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

First-Line Treatment Options

Corticosteroids

Corticosteroids are the standard initial treatment, with longer courses preferred over shorter courses. 1, 2 This remains the gold standard despite lack of high-quality randomized trials. 5, 6

Intravenous Immunoglobulin (IVIg)

IVIg at 1 g/kg as a single dose is used when rapid platelet increase is required, repeatable if necessary. 1, 2 This is particularly useful before planned procedures or in the third trimester of pregnancy with platelet counts <10,000. 1

Anti-D Immunoglobulin

Anti-D immunoglobulin is an alternative first-line option if corticosteroids are contraindicated (only in Rh-positive, non-splenectomized patients). 1

Second-Line Treatment

Splenectomy

Splenectomy is recommended for patients who have failed corticosteroid therapy and can produce long-lasting response in the majority of patients. 1, 5 The median age of splenectomized patients is significantly younger (28 years), reflecting both physician and patient reluctance due to lifelong infection risk. 7

Rituximab

Rituximab may be considered for patients at risk of bleeding who have failed first-line therapy or splenectomy. 1

Thrombopoietin Receptor Agonists (TPO-RAs)

TPO-RAs like romiplostim are recommended for patients who relapse after splenectomy or have contraindications to splenectomy. 1 Romiplostim carries risks of thrombosis, particularly when platelet counts become elevated, and requires weekly platelet monitoring with dose adjustments. 8

Critical Pitfalls to Avoid

• Never transfuse platelets in ITP without life-threatening bleeding—they are contraindicated as they will be rapidly destroyed. 2
• Do not perform routine bone marrow examination before initiating IVIg in typical ITP presentations. 1
• Avoid medications that impair platelet function (aspirin, NSAIDs) as they increase bleeding risk. 4
• Do not miss secondary causes: failure to test for HIV, HCV, H. pylori, or recognize drug-induced thrombocytopenia leads to inappropriate management. 4
• Beware of pseudothrombocytopenia: always review the peripheral smear to exclude EDTA-dependent platelet clumping before diagnosing true thrombocytopenia. 2, 4

Special Population: Pregnancy

Pregnant women with platelet counts >50,000 do not routinely require treatment. 1 Treatment is required for: 1

• Platelet counts <10,000, OR
• Platelet counts 10,000-30,000 in second or third trimester with bleeding