Can polycythemia vera be present when the hemoglobin level is below 17 g/dL?

Can Polycythemia Vera Be Present When Hemoglobin Is Below 17 g/dL?

Yes, polycythemia vera (PV) can absolutely be diagnosed with hemoglobin below 17 g/dL, particularly in women and in men with a sustained rise from baseline, and iron deficiency can mask the diagnosis entirely by lowering hemoglobin despite underlying clonal myeloproliferation. 1, 2

Sex-Specific Diagnostic Thresholds

The WHO diagnostic criteria establish different hemoglobin thresholds based on sex, making PV diagnosis possible well below 17 g/dL:

• Women: Hemoglobin ≥16.5 g/dL meets the major criterion for PV diagnosis—clearly below the 17 g/dL threshold mentioned in your question 3, 1, 2
• Men: Hemoglobin ≥18.5 g/dL is the standard threshold, but an alternative pathway exists: hemoglobin ≥17 g/dL with a documented sustained increase of ≥2 g/dL from individual baseline also satisfies the major criterion 1, 2

This alternative threshold was specifically designed to capture early or "masked" PV cases where the absolute hemoglobin has not yet reached the higher threshold but shows progressive elevation 1, 2, 4

The Critical Role of Iron Deficiency

Iron deficiency is the most important reason PV can present with hemoglobin below diagnostic thresholds:

• Iron deficiency can completely mask PV by lowering hemoglobin levels despite ongoing clonal erythroid proliferation 2, 5
• Formal WHO diagnosis requires demonstrating the hemoglobin/hematocrit criteria after iron replacement 2
• However, in routine clinical practice, a working diagnosis of PV should not be prevented by the presence of iron deficiency, even if WHO criteria are not met 2
• Iron-deficient patients with PV may present with microcytic polycythemia—elevated RBC count but paradoxically reduced hemoglobin 5

Diagnostic Algorithm When Hemoglobin Is Below 17 g/dL

Step 1: Assess sex-specific thresholds

• If female with Hb ≥16.5 g/dL → proceed immediately to JAK2 testing 1, 2
• If male with Hb 17.0–18.4 g/dL → document baseline hemoglobin and assess for sustained ≥2 g/dL rise 1, 2

Step 2: Evaluate for iron deficiency

• Order serum ferritin, transferrin saturation, and complete iron panel 2, 5
• If transferrin saturation <20% or ferritin is low, iron deficiency is masking the true red cell mass 2, 5
• Consider bone marrow biopsy showing absent iron stores as definitive evidence 2

Step 3: JAK2 mutation testing

• JAK2 V617F (exon 14) detects >90–95% of PV cases 1, 6
• If negative, test for JAK2 exon 12 mutations 3, 1
• A positive JAK2 mutation in the context of borderline hemoglobin strongly suggests PV, especially if other features are present 1, 6

Step 4: Look for supporting features

• Thrombocytosis ≥450 × 10⁹/L (present in 53% of PV) 6
• Leukocytosis ≥12 × 10⁹/L (present in 49% of PV) 6
• Splenomegaly (present in 36% of PV) 6
• Pruritus, especially aquagenic (present in 33% of PV) 6
• Low or low-normal serum erythropoietin level 3, 1

Step 5: Bone marrow biopsy if JAK2 positive

• Required to document hypercellularity with trilineage growth (panmyelosis) 3, 1
• Megakaryocyte proliferation with large, mature morphology and clustering 3
• This fulfills a minor criterion needed for diagnosis 3, 1

The "Masked" or "Latent" PV Phenomenon

Research has documented patients who initially present with borderline hemoglobin and thrombocytosis mimicking essential thrombocythemia, but later develop full-blown PV 7. In one series:

• 44 patients had sustained borderline erythrocytosis but failed to meet WHO criteria initially due to low hemoglobin 7
• 23 of these patients had thrombocytosis >600 × 10⁹/L, suggesting ET, but later developed overt PV 7
• Bone marrow histopathology showed characteristic PV features even when hemoglobin was below diagnostic thresholds 7

This underscores that PV is a bone marrow disorder, not simply a hemoglobin number—the clonal proliferation exists even when hemoglobin is suppressed by iron deficiency or other factors 7

Common Pitfalls to Avoid

• Don't dismiss PV in women with Hb 16.5–17.0 g/dL thinking it's "below 17"—this range meets WHO criteria for females 1, 2
• Don't overlook iron deficiency as a cause of falsely reassuring hemoglobin levels in true PV 2, 5
• Don't rely solely on hemoglobin when other features suggest PV (thrombocytosis, splenomegaly, pruritus, JAK2 mutation) 6, 7
• Don't use hematocrit alone as a surrogate—one study found only 35% of male PV patients had Hb >18.5 g/dL, but hematocrit ≥60% was 100% specific for absolute erythrocytosis 8

Why This Matters for Morbidity and Mortality

Missing early PV has serious consequences:

• Thrombotic risk exists even with "borderline" hemoglobin—16% of patients have arterial thrombosis and 7% have venous thrombosis at or before diagnosis 6
• Untreated patients survive only 6–18 months, whereas proper treatment extends survival to >10 years 9
• Maintaining hematocrit <45% through phlebotomy reduces thrombotic events regardless of initial hemoglobin level 6
• Early diagnosis allows initiation of aspirin and phlebotomy, which are the cornerstones of thrombosis prevention 6

The bottom line: A hemoglobin below 17 g/dL does not exclude PV, particularly in women, in men with documented rises from baseline, or in any patient with iron deficiency masking the true red cell mass. 1, 2, 7