What is the most appropriate investigation to confirm the diagnosis in a 6-year-old boy with a pale appearance, ecchymosis, and petechiae, who presented 2 weeks after an upper respiratory infection, and has thrombocytopenia (low platelet count)?

Peripheral Blood Smear is the Most Appropriate Investigation

The peripheral blood smear (option C) is the most appropriate investigation to confirm the diagnosis of immune thrombocytopenic purpura (ITP) in this 6-year-old boy. 1

Clinical Context and Diagnosis

This child presents with the classic triad of ITP:

• Post-viral illness (upper respiratory infection 2 weeks ago) 2, 3
• Isolated thrombocytopenia (low platelet count) 1
• Bleeding manifestations limited to skin (petechiae and ecchymosis) 4

The child is now well-appearing with only skin findings, which is typical for pediatric ITP 4.

Why Peripheral Blood Smear is the Correct Answer

The peripheral blood smear serves multiple critical diagnostic functions that make it the cornerstone investigation: 1

• Confirms true thrombocytopenia by excluding pseudothrombocytopenia (EDTA-dependent platelet clumping that falsely lowers automated counts) 1, 5
• Identifies characteristic ITP features including normal-sized or slightly enlarged platelets, normal red blood cell morphology, and normal white blood cell morphology 1
• Excludes alternative diagnoses by ruling out schistocytes (thrombotic microangiopathy), giant platelets (inherited thrombocytopenias), immature white cells (leukemia), or other abnormalities 4, 1

The American Society of Hematology guidelines explicitly state that a complete blood count and examination of the peripheral blood smear are essential in ITP and form the cornerstone of diagnosis 1.

Why the Other Options Are Incorrect

Coagulation Factors (Option A)

• ITP is a disorder of platelet destruction, not coagulation factor deficiency 1
• Coagulation studies (PT, aPTT, fibrinogen) would be normal in ITP 5
• These tests are only indicated if disseminated intravascular coagulation is suspected, which this child does not have 5

Bone Marrow Biopsy (Option B)

• Bone marrow examination is NOT necessary in children with typical ITP features 4, 1
• The American Society of Hematology explicitly recommends against routine bone marrow examination in children presenting with typical ITP (grade 1B recommendation) 4
• Bone marrow is only indicated when atypical features are present, such as: 4, 1
  • Abnormalities beyond isolated thrombocytopenia (pancytopenia, abnormal white cell count)
  • Systemic symptoms (fever, weight loss, bone pain)
  • Lymphadenopathy or hepatosplenomegaly
  • Abnormal peripheral smear findings
  • Age ≥60 years (not applicable to children)

Anti-Platelet Antibodies (Option D)

• The American Society of Hematology found insufficient evidence to recommend routine use of antiplatelet antibodies in the evaluation of children with suspected ITP 4
• These antibodies do not change management and are not necessary for diagnosis 1
• ITP remains a diagnosis of exclusion based on clinical features and peripheral smear, not antibody testing 1

Diagnostic Algorithm for This Patient

1. Obtain peripheral blood smear immediately to confirm isolated thrombocytopenia and exclude alternative diagnoses 1

2. Verify typical ITP features on smear: 1

   • Normal or slightly enlarged platelets (NOT giant platelets)
   • Normal red blood cell morphology (no schistocytes)
   • Normal white blood cell morphology (no immature cells)

3. Confirm clinical features are typical: 4

   • Isolated thrombocytopenia on CBC
   • No fever, lymphadenopathy, hepatosplenomegaly
   • Bleeding limited to skin manifestations
   • Otherwise healthy child

4. If all features are typical, diagnose ITP without bone marrow examination 4

Management Implications

Since this child is now well-appearing with only skin manifestations (petechiae and ecchymosis), observation alone is recommended regardless of platelet count (grade 1B recommendation) 4. The American Society of Hematology explicitly states that children with no bleeding or mild bleeding (defined as skin manifestations only, such as bruising and petechiae) should be managed with observation alone 4.

Critical Pitfalls to Avoid

• Never diagnose ITP without personally reviewing the peripheral blood smear, as automated counts can miss pseudothrombocytopenia, giant platelets, or schistocytes 1
• Do not perform bone marrow biopsy in children with typical ITP features, as this exposes the child to unnecessary procedural risk without diagnostic benefit 4
• Do not rely on antiplatelet antibody testing, as it has insufficient evidence for routine diagnostic use and does not change management 4, 1
• Reassess the diagnosis if atypical features develop during monitoring, such as abnormalities in white blood cell count, lymphadenopathy, or multiple cytopenias 4, 1