In a 6‑year‑old boy with recent upper respiratory infection, pallor, ecchymoses, petechiae and thrombocytopenia, what is the most appropriate investigation to confirm the diagnosis?

Peripheral Blood Smear is the Most Appropriate Investigation

In a 6-year-old boy with thrombocytopenia, petechiae, and ecchymoses following an upper respiratory infection 2 weeks ago, a peripheral blood smear reviewed by a hematologist is the most appropriate investigation to confirm the diagnosis of immune thrombocytopenic purpura (ITP). 1, 2

Why Peripheral Blood Smear is Essential

The peripheral blood smear serves three critical diagnostic functions that make it the cornerstone test for confirming ITP:

• Confirms true thrombocytopenia by excluding pseudothrombocytopenia (EDTA-dependent platelet clumping), which occurs in approximately 0.1% of samples and can falsely lower automated platelet counts 3, 1, 2

• Identifies characteristic ITP features including normal-sized or only mildly enlarged platelets (not giant platelets approaching red blood cell size), normal red blood cell morphology without schistocytes, and normal white blood cell morphology without immature or abnormal cells 3, 1, 2

• Excludes life-threatening alternative diagnoses such as thrombotic thrombocytopenic purpura (TTP), which shows schistocytes and carries >90% mortality if untreated, leukemia or myelodysplastic syndrome (immature white cells or blasts), and inherited thrombocytopenias like MYH9-related disease (giant platelets and leukocyte inclusion bodies) 1, 4

Why the Other Options Are Incorrect

Coagulation Factors (Option A)

• ITP is a disorder of platelet destruction, not coagulation factor deficiency 1
• PT, aPTT, fibrinogen, and INR remain normal in ITP; abnormal coagulation studies would suggest disseminated intravascular coagulation (DIC) or other consumptive coagulopathies 1
• Coagulation studies do not confirm ITP diagnosis and are only indicated when DIC is suspected clinically 1

Bone Marrow Biopsy (Option B)

• Bone marrow examination is not necessary in children with typical ITP features 3, 1, 2
• This child presents with classic ITP: isolated thrombocytopenia 2 weeks post-viral upper respiratory infection, now well with only skin manifestations (petechiae and ecchymoses), and no fever, lymphadenopathy, hepatosplenomegaly, or systemic symptoms 3, 2
• Bone marrow biopsy is only indicated when atypical features are present: age ≥60 years, systemic symptoms (fever, weight loss, bone pain), abnormal CBC parameters beyond isolated thrombocytopenia (unexplained anemia or leukopenia), atypical peripheral smear findings (schistocytes, immature cells, giant platelets), organomegaly or lymphadenopathy on exam, or failure to respond to first-line ITP therapies 3, 1
• In a study of 127 consecutive children with suspected ITP who underwent bone marrow aspiration, other causes were identified in only 5 (4%) children, all of whom had atypical presenting features 3
• Performing unnecessary bone marrow biopsy exposes the child to procedural morbidity (pain, bleeding risk, infection risk) without diagnostic benefit when typical ITP features are present 1, 2

Anti-Platelet Antibodies (Option D)

• Platelet-associated IgG and glycoprotein-specific antiplatelet antibodies have insufficient evidence for routine diagnostic use in ITP 3, 1
• These antibodies are elevated in both immune and non-immune thrombocytopenia, making them non-discriminatory 1
• Antiplatelet antibody testing does not change management and should not be ordered routinely 3, 1

Clinical Context Supporting ITP Diagnosis

This presentation is classic for pediatric ITP:

• Age 6 years falls within the peak incidence (2-5 years, though any pediatric age may be affected) 5
• Preceding upper respiratory infection 2 weeks ago matches the typical 1-4 week interval before ITP onset seen in 50-60% of pediatric cases 6, 5
• Now well with only skin manifestations (petechiae and ecchymoses) indicates no active bleeding or systemic illness, which is typical for ITP 2
• Isolated thrombocytopenia without fever, organomegaly, or other cytopenias strongly suggests primary ITP 3, 1, 2

Diagnostic Algorithm for This Patient

1. Obtain peripheral blood smear reviewed by a hematopathologist to confirm isolated thrombocytopenia, verify typical ITP features (normal or mildly enlarged platelets, normal RBC and WBC morphology), and exclude alternative diagnoses (no schistocytes, no giant platelets, no immature white cells) 1, 2

2. Verify clinical features are typical: isolated thrombocytopenia on CBC, no fever, no lymphadenopathy or hepatosplenomegaly on physical exam, and bleeding limited to skin manifestations only 1, 2

3. If peripheral smear confirms typical ITP features and physical exam is normal except for bleeding manifestations, diagnose ITP without bone marrow examination 3, 1, 2

Management Implications

• Observation alone is recommended for children with no bleeding or mild bleeding (skin manifestations only such as petechiae and ecchymoses), regardless of platelet count 3, 2
• Treatment should only be initiated if clinically significant mucosal bleeding occurs (epistaxis requiring intervention, oral bleeding, gastrointestinal or genitourinary bleeding), not based on platelet number alone 3, 2
• Most pediatric ITP cases resolve spontaneously within 6 months; two-thirds of children recover without treatment 3, 5

Critical Pitfalls to Avoid

• Never diagnose ITP without personally reviewing the peripheral blood smear, as automated counters miss pseudothrombocytopenia, giant platelets, and schistocytes 1, 2
• Missing schistocytes on smear delays recognition of TTP, which requires immediate plasma exchange to prevent >90% mortality 4
• Performing bone marrow biopsy in children with typical ITP features exposes the child to unnecessary procedural risk without diagnostic benefit 1, 2
• Relying on antiplatelet antibody testing wastes resources and does not change management 3, 1