In India, what hemoglobin levels (men >16.5 g/dL, women >16.0 g/dL) warrant evaluation for polycythemia vera?

Hemoglobin Thresholds for Polycythemia Vera Evaluation in India

In India, hemoglobin levels >16.5 g/dL in men and >16.0 g/dL in women warrant evaluation for polycythemia vera according to the WHO 2016 diagnostic criteria. 1

WHO 2016 Diagnostic Thresholds

The 2016 WHO revision lowered the hemoglobin thresholds specifically to capture "masked PV" cases that were previously missed:

• Men: Hemoglobin >16.5 g/dL or hematocrit >49% 1
• Women: Hemoglobin >16.0 g/dL or hematocrit >48% 1

These thresholds represent the first major criterion for PV diagnosis and trigger the need for JAK2 mutation testing. 2

Diagnostic Algorithm at These Thresholds

When hemoglobin meets these levels, the following systematic evaluation is mandatory:

Step 1: JAK2 Mutation Testing (First-Line)

• JAK2 V617F testing should be ordered immediately, as it detects >90–95% of PV cases 2
• If JAK2 V617F is negative, JAK2 exon 12 mutation analysis must be performed, accounting for an additional 2–3% of cases 2

Step 2: Complete Diagnostic Criteria

To confirm PV, you need either:

Pathway A: Both major criteria + ≥1 minor criterion 1, 2

• Elevated Hb/Hct (>16.5/49% men; >16.0/48% women)
• JAK2 mutation present
• PLUS at least one of: low serum EPO, bone marrow hypercellularity, or endogenous erythroid colonies

Pathway B: First major criterion + ≥2 minor criteria 2

• Elevated Hb/Hct
• PLUS two of: low serum EPO, bone marrow hypercellularity, or endogenous erythroid colonies
• (Used when JAK2 is negative)

Step 3: Supporting Laboratory Tests

• Serum erythropoietin: Subnormal levels serve as a minor criterion 2
• Complete blood count with differential: Assess for thrombocytosis and leukocytosis 3
• Iron studies: Ferritin and transferrin saturation to exclude iron deficiency masking higher hemoglobin 2
• Bone marrow biopsy: Shows hypercellularity with trilineage growth and pleomorphic megakaryocytes (minor criterion) 1, 4

Clinical Impact of the 2016 Revision in India

The lowered thresholds substantially increased PV case detection. An Indian study demonstrated that among patients with hemoglobin below the old WHO 2008 thresholds (men <18.5 g/dL, women <16.5 g/dL) but meeting the new 2016 criteria, 9.8% were diagnosed with PV—a rate that cannot be dismissed. 4 This contrasts with 65% PV diagnosis rate in patients meeting the higher thresholds. 5

The study emphasized that the 2016 revision is particularly important for detecting "masked PV" cases in India, where patients present with hemoglobin levels in the 16.0–18.4 g/dL range for men and 15.0–16.4 g/dL range for women but still harbor JAK2 mutations and characteristic bone marrow findings. 4, 6

Critical Pitfalls to Avoid

Do Not Diagnose PV on Low EPO Alone

• Low serum EPO is only a minor criterion and cannot establish PV diagnosis independently 2
• In a patient with hemoglobin 16.0 g/dL and low EPO, the mandatory next step is JAK2 mutation testing, followed by systematic exclusion of secondary erythrocytosis if JAK2 is negative 2

Do Not Overlook Iron Deficiency

• Iron deficiency can mask true erythrocytosis by lowering hemoglobin while red cell mass remains elevated 2
• Formal PV diagnosis should be deferred until after iron replacement therapy allows hemoglobin to reach diagnostic levels 2
• Check ferritin and transferrin saturation in all cases 3

Do Not Apply Standard Thresholds at High Altitude

• Physiologic adaptation to altitude increases hemoglobin by 0.2–4.5 g/dL depending on elevation (1,000–4,500 meters) 7
• WHO criteria specifically state thresholds should be adjusted for altitude of residence 7

When to Refer to Hematology

Immediate hematology referral is indicated when:

• JAK2 mutation is positive 3
• Hemoglobin >20 g/dL with hyperviscosity symptoms (headache, visual disturbances, dizziness) 3
• Unexplained splenomegaly with elevated blood counts 3
• Unusual site thrombosis (portal vein, hepatic vein, cerebral sinus) even with normal blood counts 8

Evidence Strength and Nuances

The WHO 2016 criteria represent strong guideline recommendations from the European LeukemiaNet published in Leukemia (2018). 1 The lowered thresholds are supported by research demonstrating that 35% of JAK2-mutated PV patients present with hemoglobin below the old WHO 2008 thresholds, and these "masked PV" patients have worse overall survival compared to overt PV (P=0.011). 6

However, applying these lower thresholds in the general population without clinical context can lead to substantial overinvestigation: in one study of 248,839 outpatients with normal complete blood counts, 5.99% of men and 0.22% of women met the new hemoglobin thresholds. 9 Therefore, diagnostic workup should be pursued when these hemoglobin levels are accompanied by clinical features such as thrombocytosis, leukocytosis, splenomegaly, aquagenic pruritus, or unusual thrombosis. 9