What is the best course of action for a 10-year-old patient with elevated absolute eosinophil (EOS) and basophil counts, normal white blood cell (WBC) count, anemia (low hematocrit), and thrombocytopenia with low mean platelet volume (MPV)?

Urgent Hematology Referral and Systematic Evaluation for Possible Myeloproliferative Disorder

This 10-year-old requires immediate hematology referral to exclude chronic myeloid leukemia (CML) or other myeloproliferative neoplasms, given the combination of elevated eosinophils, elevated basophils, anemia, and thrombocytopenia with low mean platelet volume. 1, 2

Critical Red Flags in This Presentation

• The combination of elevated eosinophils AND elevated basophils is highly concerning for a myeloproliferative disorder, particularly CML, which characteristically presents with both cell line elevations 1, 2
• Low mean platelet volume (MPV) with thrombocytopenia suggests bone marrow hypoplasia, cytotoxic drug effect, or myelosuppressive disease, which distinguishes this from hyperdestructive thrombocytopenia (which would show high MPV) 3, 4
• The anemia combined with these findings raises concern for bone marrow involvement rather than a reactive process 2, 5

Immediate Diagnostic Workup Required

First-Line Essential Testing

• Peripheral blood smear with manual differential to assess for left shift, immature myeloid cells, dysplasia, or atypical cells that automated counts may miss 6, 2
• Serum tryptase and vitamin B12 levels, which are elevated in myeloproliferative variants of hypereosinophilia 2, 5
• Absolute eosinophil count and absolute basophil count to quantify the degree of elevation, as percentages alone can be misleading 7, 6

Specialized Hematology Testing

• Bone marrow aspirate and biopsy with immunohistochemistry for CD117, CD25, and tryptase to diagnose myeloproliferative disorders 2
• Cytogenetic analysis with minimum 15 metaphases to detect chromosomal abnormalities characteristic of CML (Philadelphia chromosome/BCR-ABL1) 1, 2
• FISH and/or RT-PCR for tyrosine kinase fusion genes, particularly PDGFRA, PDGFRB, FGFR1, and PCM1-JAK2, as these predict response to targeted therapy with imatinib 1, 2

Secondary Causes That Must Be Excluded

Parasitic Infection Evaluation

• Three separate concentrated stool specimens for ova and parasites 7, 2
• Strongyloides serology and culture, as this helminth can persist lifelong and cause fatal hyperinfection syndrome if immunosuppression is initiated 7, 2
• Detailed travel history focusing on fresh water exposure in Africa/tropical regions and raw/undercooked meat consumption, as helminth infections account for 19-80% of eosinophilia in endemic-exposed patients 7, 2

Critical caveat: Many helminth-infected patients do not have eosinophilia, so normal eosinophil counts do not exclude parasitic infection 7

Other Reactive Causes to Consider

• Medication review for drug-induced eosinophilia and thrombocytopenia 7, 8
• Quantitative serum immunoglobulin levels including IgE to assess for allergic/atopic conditions 2, 8

Assessment for End-Organ Damage

Given the severity of cytopenias, evaluate for eosinophil-mediated organ injury:

• Cardiac evaluation: ECG, cardiac troponin, and NT-proBNP to screen for myocardial injury 7
• Echocardiography if cardiac biomarkers elevated or symptoms present 7
• Chest X-ray to identify pulmonary infiltrates 7

Most Likely Differential Diagnoses

Primary (Neoplastic) Causes - Highest Priority

1. Chronic myeloid leukemia (CML): The combination of elevated eosinophils, elevated basophils, and cytopenias is classic for CML 1, 2
2. Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase fusion genes: These respond to imatinib therapy 1, 2
3. Idiopathic hypereosinophilic syndrome: Diagnosis of exclusion after ruling out secondary causes and neoplasms 8, 5

Secondary (Reactive) Causes - Must Exclude First

1. Helminth infection: Most common identifiable cause in endemic-exposed populations 7, 2
2. Drug-induced: Common cause of combined eosinophilia and thrombocytopenia 8, 4
3. Allergic/atopic disease: Most common cause in North America when parasites excluded 8

Management Algorithm

If Myeloproliferative Disorder Confirmed

• Imatinib is first-line therapy for CML and myeloid neoplasms with PDGFRA/PDGFRB rearrangements 1, 2
• Molecular monitoring for minimal residual disease is required 2

If Secondary Eosinophilia Identified

• Treat the underlying cause (antiparasitic therapy for helminths, discontinue offending medications) 7, 2
• Do NOT initiate corticosteroids until parasitic causes (especially Strongyloides) are excluded, as immunosuppression can cause fatal hyperinfection syndrome 7, 9

If Parasitic Infection Confirmed

• Ivermectin 200 μg/kg daily for 2 days for Strongyloidiasis 7
• Albendazole 400 mg twice daily for 3 days for Ascaris/hookworm 7
• Praziquantel 40 mg/kg single dose for Schistosomiasis 7

Critical Pitfalls to Avoid

• Do not delay hematology referral while pursuing parasitic workup, as these evaluations should occur simultaneously 2, 10
• Do not start corticosteroids empirically before excluding Strongyloides, as this can be fatal 7, 9
• Do not rely solely on automated CBC differentials, as they may miss critical findings like immature cells or dysplasia 6, 2
• Do not assume normal eosinophil counts exclude parasitic infection in patients with travel history 7
• Do not overlook the significance of low MPV, which suggests bone marrow pathology rather than peripheral destruction 3, 4

Monitoring During Workup

• Assess bleeding risk: Platelet counts <50 × 10³/μL require activity restrictions to avoid trauma-associated bleeding 4
• Platelet transfusion indicated if active hemorrhage or platelet count <10 × 10³/μL 4
• Serial CBC monitoring to assess progression while awaiting specialized testing results 2, 10