Diagnostic Hemoglobin, Hematocrit, and RBC Levels for Polycythemia Vera
For diagnosing primary polycythemia vera, hemoglobin must be ≥18.5 g/dL in men or ≥16.5 g/dL in women, OR hematocrit >99th percentile for age/sex/altitude, OR hemoglobin ≥17 g/dL in men or ≥15 g/dL in women with a sustained increase of ≥2 g/dL from baseline. 1
Primary Diagnostic Thresholds
Standard Hemoglobin Criteria
Alternative Hemoglobin Criteria (Early/Masked PV)
- Men: Hemoglobin ≥17 g/dL with documented sustained increase of ≥2 g/dL from individual baseline (not attributable to iron deficiency correction) 1
- Women: Hemoglobin ≥15 g/dL with documented sustained increase of ≥2 g/dL from individual baseline (not attributable to iron deficiency correction) 1
Hematocrit Criteria
- Hematocrit >99th percentile of method-specific reference range adjusted for age, sex, and altitude of residence 1
- This accommodates centers using hematocrit as their primary polycythemia assessment tool 1
Red Cell Mass
- Elevated red cell mass >25% above mean normal predicted value 1
- This provides an alternative when hemoglobin/hematocrit values are discordant 1
Critical Diagnostic Algorithm
The WHO criteria require BOTH major criteria plus ≥1 minor criterion, OR the first major criterion plus ≥2 minor criteria. 1
Major Criteria
- Meeting any of the hemoglobin/hematocrit/RBC mass thresholds above 1
- Presence of JAK2 V617F or JAK2 exon 12 mutation 1, 2
Minor Criteria
- Bone marrow biopsy showing hypercellularity for age with trilineage growth (panmyelosis) with prominent erythroid, granulocytic, and megakaryocytic proliferation 1, 2
- Serum erythropoietin level below the reference range for normal 1, 2
- Endogenous erythroid colony formation in vitro 1, 2
Important Clinical Caveats
Iron Deficiency Confounding
- Iron deficiency lowers hemoglobin levels and can mask PV diagnosis 1
- For research/clinical trials: Formal PV diagnosis requires demonstrating WHO hemoglobin/hematocrit criteria AFTER iron replacement 1
- For routine clinical practice: You should not be prevented from making a working diagnosis of PV in the presence of iron deficiency, even if WHO criteria are not met 1
- This pragmatic approach recognizes that waiting for iron repletion may delay critical treatment 1
Masked Polycythemia Vera Recognition
- Approximately 15-35% of PV patients present with hemoglobin below the traditional 18.5/16.5 g/dL thresholds 3
- These "masked PV" patients have worse overall survival compared to overt PV (P=0.011 by WHO criteria, P=0.0019 by BCSH criteria) 3
- The revised criteria specifically capture these early cases through the alternative hemoglobin thresholds (17 g/dL men, 15 g/dL women with sustained 2 g/dL increase) 1
- Risk factors for inferior survival in masked PV include age >65 years and white blood cell count >15 × 10⁹/L 3
Pediatric-Specific Adjustments
- Must use age-appropriate hemoglobin/hematocrit thresholds - adult cutoffs will miss pediatric cases 2
- Hemoglobin/hematocrit >99th percentile for age, sex, and altitude is the appropriate criterion 2
- Mandatory exclusion of secondary causes (congenital heart disease, chronic lung disease, high altitude) before diagnosing pediatric PV 2
Practical Pitfalls to Avoid
- The isolated use of borderline hemoglobin/hematocrit levels without supporting clinical/laboratory features leads to unnecessary diagnostic workups 4
- In a general population study, 5.99% of men had Hb >165 g/L and 0.22% of women had Hb >160 g/L, emphasizing the need for additional diagnostic criteria beyond hemoglobin alone 4
- Always assess for JAK2 mutations and consider bone marrow biopsy when hemoglobin/hematocrit are in diagnostic range 5, 6
- Patients can present with unusual site thrombosis (splanchnic veins) and normal blood counts but still have underlying PV 5, 7