What is the appropriate management for a pediatric patient under 10 years old presenting with erythrocytosis, hyperhemoglobinemia, elevated hematocrit, leukopenia, and lymphocytosis?

Management of Pediatric Erythrocytosis with Leukopenia and Lymphocytosis

Immediate Action Required

This constellation of findings—erythrocytosis, elevated hematocrit, leukopenia with lymphocytosis—demands urgent peripheral blood smear review and immediate hematology/oncology consultation, as the combination raises serious concern for hematologic malignancy or complex myeloproliferative disorder. 1, 2

Critical First Steps

Obtain Peripheral Blood Smear Immediately

• The peripheral blood smear is the single most important test to differentiate benign from malignant causes and must be reviewed by an experienced pathologist or hematologist to identify blasts, atypical lymphocytes, or immature cells 1, 2
• Contact pediatric hematology/oncology for same-day consultation if blasts or immature cells are present 1
• The presence of blasts or immature cells on peripheral smear mandates immediate hematology/oncology referral without waiting for additional testing 1

Assess for Red Flag Clinical Features

• Check for constitutional symptoms: fever, night sweats, weight loss, decreased appetite, or severe fatigue (severity scale 7-10/10) 1, 2
• Examine for organomegaly (splenomegaly, hepatomegaly), lymphadenopathy, petechiae, ecchymoses, or bleeding signs—any of these warrant immediate hematology referral 1, 2
• Document extremity or joint pain, which may be the only presenting symptom of leukemia in children 2
• Note that approximately 20% of children with chronic myeloid leukemia present with bleeding signs despite normal platelet counts 1

Essential Laboratory Workup

Baseline Metabolic Assessment

• Order complete metabolic panel to assess for tumor lysis syndrome parameters: uric acid, LDH, potassium, phosphate, and calcium 1, 2
• These parameters indicate rapid cell turnover in leukemia and guide urgent management 1

Determine Absolute Cell Counts

• Calculate absolute lymphocyte count and identify if other cell lines are affected through complete blood count with differential 2
• The combination of erythrocytosis with leukopenia is highly unusual and suggests either a complex myeloproliferative disorder or overlapping conditions 3, 4

Differential Diagnosis Considerations

Malignancy Must Be Excluded First

• Acute lymphoblastic leukemia (ALL) should be considered if peripheral smear shows ≥20% lymphoblasts or ≥1,000 circulating lymphoblasts/µL 1, 2
• Chronic myeloid leukemia (CML) should be suspected with high leukocyte counts and constitutional symptoms; order BCR::ABL1 fusion gene testing and Philadelphia chromosome analysis 1, 2
• Pediatric CML can present with extreme thrombocytosis without neutrophilia, basophilia, or eosinophilia, simulating other myeloproliferative disorders 5

Secondary Erythrocytosis Evaluation (Only After Malignancy Excluded)

• Secondary erythrocytosis is driven by hormonal factors (predominantly erythropoietin) extrinsic to the erythroid compartment and may represent physiologic response to tissue hypoxia or abnormal autonomous erythropoietin production 3, 4
• Congenital secondary erythrocytoses are caused by hemoglobin variants with increased oxygen affinity (HBB, HBA mutations), 2,3-bisphosphoglycerate deficiency (BPGM mutations), or mutations in hypoxia sensing pathway genes (VHL, EPAS1, EGLN1) 3, 6
• Primary familial and congenital polycythemia due to erythropoietin receptor gene mutations presents with low erythropoietin levels 3, 6

Management Algorithm

If Blasts Present on Smear

• Refer immediately to hematology/oncology without delay for additional testing 1, 2
• Do not wait for molecular testing results before referral 1

If Constitutional Symptoms Present

• Immediate hematology/oncology referral is required even without blasts on smear, given the severity of presentation with multiple cytopenias 1, 2

If Smear Shows No Blasts and No Constitutional Symptoms

• Repeat CBC in 1-2 weeks to ensure resolution or progression 2
• Persistent abnormalities on repeat testing mandate hematology consultation 2
• Continue monitoring for development of new symptoms: fever, fatigue, bleeding, or organomegaly 2

Critical Pitfalls to Avoid

• Do not delay hematology referral while pursuing extensive workup for secondary causes of erythrocytosis—the combination with leukopenia and lymphocytosis is atypical and requires expert evaluation 1, 2
• Do not assume reactive lymphocytosis from infection without peripheral smear review, as this could delay diagnosis of acute leukemia 1, 2
• The molecular causes of congenital erythrocytosis remain unidentified in approximately 70% of patients, so negative genetic testing does not exclude the diagnosis 6
• In children under 10 years old, bone marrow examination is not necessary for typical presentations but may be required based on hematology/oncology assessment 7