What is the most appropriate investigation to confirm the diagnosis in a child with thrombocytopenia, ecchymosis, and petechiae following an upper respiratory infection?

Most Appropriate Investigation: Peripheral Blood Smear

The most appropriate investigation to confirm the diagnosis in this 6-year-old boy with post-infectious thrombocytopenia is a peripheral blood smear (Option C). 1

Diagnostic Rationale

Why Peripheral Blood Smear is Essential

A complete blood count and examination of the peripheral blood smear are essential in ITP and form the cornerstone of diagnosis. 1 The clinical presentation—a previously healthy child with petechiae and ecchymosis following an upper respiratory infection 2 weeks ago—is classic for immune thrombocytopenic purpura (ITP). 1

The peripheral blood smear serves multiple critical diagnostic functions:

• Confirms true thrombocytopenia by excluding pseudothrombocytopenia (EDTA-dependent platelet clumping), which can falsely lower automated platelet counts 1, 2
• Identifies characteristic ITP features: normal-sized or slightly larger platelets (but not giant platelets approaching RBC size), normal RBC morphology, and normal WBC morphology 1
• Excludes alternative diagnoses such as leukemia, aplastic anemia, or thrombotic microangiopathies that would show abnormal cells, schistocytes, or other morphologic abnormalities 1, 3

Why Other Options Are NOT Appropriate

Bone marrow biopsy (Option B) is NOT necessary in children with typical ITP features. 1 In a study of 127 consecutive children with suspected ITP who underwent bone marrow aspirations, other causes were identified in only 5 (4%) children, and all had atypical presenting features. 1 The 2011 ASH guidelines represent a major change from 1996, explicitly stating that bone marrow examination is no longer considered necessary at diagnosis in children with typical presentations. 1

Bone marrow examination is only indicated when:

• Atypical features are present (abnormal hemoglobin, WBC count, or morphology) 1, 3
• Fever, bone/joint pain, or systemic symptoms exist 1
• Lymphadenopathy or hepatosplenomegaly is found 1
• Age >60 years (not applicable here) 3, 2
• Failure to respond to initial therapy 1, 3

Coagulation factors (Option A) are not indicated because ITP is a disorder of platelet destruction, not coagulation factor deficiency. 1 Coagulation studies would be normal in ITP and are only useful if disseminated intravascular coagulation is suspected. 3, 2

Anti-platelet antibodies (Option D) have insufficient evidence for routine diagnostic use. 1 The ASH guidelines found insufficient evidence to recommend routine use of antiplatelet antibodies in evaluating children with suspected ITP. 1 These tests have poor sensitivity and specificity and do not change management. 1

Diagnostic Algorithm for This Patient

Step 1: Confirm Diagnosis with Peripheral Blood Smear

• Review smear for platelet size and morphology (should show normal to slightly large platelets) 1
• Verify normal RBC and WBC morphology 1
• Exclude pseudothrombocytopenia, schistocytes, or abnormal cells 1, 3, 2

Step 2: Assess Bleeding Severity

At presentation, determine if the child has:

• No bleeding or minor purpura only → observation without treatment 1, 2
• Moderate mucous membrane bleeding → consider treatment 1
• Severe life-threatening bleeding → immediate hospitalization and treatment 1

Step 3: Additional Testing (Only if Indicated)

Since this child is "now well" with only skin findings, additional testing is generally NOT needed. 1 However, consider:

• HIV testing only if risk factors present 1
• Testing for other secondary causes only if atypical features develop 1

Critical Pitfalls to Avoid

• Do not perform bone marrow biopsy routinely in children with typical ITP presentation—this represents outdated practice from pre-2011 guidelines 1
• Do not order antiplatelet antibody testing as it lacks diagnostic utility and will not change management 1
• Do not miss pseudothrombocytopenia by failing to review the peripheral smear—this can lead to unnecessary treatment 1, 3, 2
• Do not overlook atypical features on the smear (schistocytes, abnormal WBCs, giant platelets) that would mandate further investigation 1, 3

Management Implications

Since the child is now well with only skin manifestations, observation alone is appropriate regardless of platelet count if there is no active bleeding or only minor purpura. 1, 2 Most pediatric ITP cases (60-80%) resolve spontaneously within 6 months. 2, 4 Treatment should only be initiated if clinically significant bleeding occurs, not based on platelet number alone. 1, 2