Diagnostic Criteria for Polycythemia Vera in Pediatrics
The WHO diagnostic criteria for polycythemia vera apply to pediatric patients with age-appropriate adjustments for hemoglobin/hematocrit thresholds, requiring either both major criteria plus one minor criterion, or the first major criterion plus two minor criteria. 1, 2
Major Criteria
Elevated hemoglobin or hematocrit: Hemoglobin ≥18.5 g/dL in men or ≥16.5 g/dL in women, OR hemoglobin/hematocrit >99th percentile of method-specific reference range for age, sex, and altitude of residence 1, 2
- The age-specific adjustment is critical in pediatrics, as normal hemoglobin values vary significantly throughout childhood 1
- Alternative evidence includes hemoglobin ≥17 g/dL in men or ≥15 g/dL in women with documented sustained increase of ≥2 g/dL from baseline that cannot be attributed to iron deficiency correction 1
- Elevated red cell mass >25% above mean normal predicted value can substitute for hemoglobin/hematocrit criteria 1
Presence of JAK2 mutation: JAK2 V617F or JAK2 exon 12 mutation 1, 2
- Critical pediatric caveat: JAK2 V617F mutation is significantly less frequent in pediatric PV compared to adults (found in >90% of adult PV but lower rates in children) 1, 3
- When JAK2 V617F is negative in children, testing for JAK2 exon 12 mutations is essential 2, 3
- PRV-1 RNA overexpression is the most common myeloproliferative marker in pediatric PV patients who are JAK2-negative 3
Bone marrow biopsy: Hypercellularity for age with trilineage growth (panmyelosis) showing prominent erythroid, granulocytic, and megakaryocytic proliferation with pleomorphic, mature megakaryocytes 1, 2
Minor Criteria
Subnormal serum erythropoietin level below the reference range for normal 1, 2
Endogenous erythroid colony formation in vitro 1
Bone marrow biopsy (when used as minor criterion if not already used as major criterion) 1
Diagnostic Algorithm
Pathway 1: Both major criteria (elevated hemoglobin/hematocrit + JAK2 mutation) plus one minor criterion 1, 2
Pathway 2: First major criterion (elevated hemoglobin/hematocrit) plus two minor criteria—this pathway captures JAK2-negative cases or those with low mutational burden 1, 2
Critical Pediatric-Specific Considerations
Lower JAK2 mutation frequency: Pediatric PV has significantly lower JAK2 V617F positivity than adult PV, making bone marrow biopsy and additional minor criteria more important for diagnosis 3
Mandatory exclusion of secondary causes: Rule out secondary erythrocytosis from congenital heart disease, chronic lung disease, sleep apnea, high altitude, renal tumors, hepatocellular carcinoma, hemoglobin variants with increased oxygen affinity, 2,3-bisphosphoglycerate deficiency, and von Hippel-Lindau mutations 2, 4
Iron deficiency confounding: Iron deficiency lowers hemoglobin levels and can mask PV; formal diagnosis requires demonstrating WHO criteria after iron replacement, though working diagnosis can proceed in clinical practice 1, 2
Familial forms: Consider primary familial and congenital polycythemia (PFCP) due to erythropoietin receptor gene mutations, which presents differently than sporadic PV 4
Thrombotic risk assessment: Pediatric PV patients have significantly lower incidence of thrombosis than adults, but Budd-Chiari syndrome occurs with particular frequency in young patients (7/35 cases in one series) 5, 3
- Leukocytosis >15 × 10⁹/L is associated with thromboembolic or hemorrhagic complications in pediatric patients 5
Common Pitfalls
Assuming adult JAK2 mutation rates apply: The significantly lower JAK2 positivity in pediatric PV means more reliance on bone marrow histology and low erythropoietin levels for diagnosis 3
Missing familial forms: Always obtain family history, as familial ET and PFCP have different pathogenetic mechanisms and may not show JAK2 mutations 4, 3
Overlooking age-specific hemoglobin thresholds: Using adult cutoffs will miss pediatric cases; always use 99th percentile for age and sex 1, 2