Is a hemoglobin level of 17.5 g/dL normal in a female, and what evaluation is recommended?

Hemoglobin 17.5 g/dL in a Female: Evaluation and Management

A hemoglobin of 17.5 g/dL in a female is elevated and requires evaluation for polycythemia vera (PV), as this exceeds the normal upper limit of 15.5 g/dL and approaches the WHO diagnostic threshold of 16.0 g/dL for PV. 1, 2

Is This Level Normal?

• No, this is not normal. The standard hemoglobin reference range for adult females is 12.0–15.5 g/dL, making 17.5 g/dL clearly elevated. 2
• The WHO 2016 criteria define one major criterion for PV as hemoglobin >16.0 g/dL in women, and this patient's value of 17.5 g/dL exceeds that threshold. 1
• While altitude and smoking can increase hemoglobin (altitude adjusts by 0.2–1.9 g/dL depending on elevation, smoking by 0.3–1.0 g/dL), these factors rarely account for hemoglobin this high in females. 2, 3

Recommended Evaluation

First-Line Testing

Order the following tests immediately to evaluate for polycythemia vera:

• JAK2 V617F mutation testing – present in approximately 95% of PV cases and is a major WHO diagnostic criterion. 1, 4
• Serum erythropoietin (EPO) level – a subnormal EPO (<10 mU/mL) is a minor WHO criterion for PV and has >90% specificity for the diagnosis. 1, 5
• Complete iron studies including serum ferritin, transferrin saturation, serum iron, and total iron-binding capacity – iron deficiency can mask PV by preventing hemoglobin from rising even higher. 5
  • Ferritin should be >100 µg/dL and transferrin saturation >20% to exclude iron deficiency. 5

Second-Line Testing (If JAK2 V617F Negative)

• JAK2 exon 12 mutation testing – accounts for approximately 3% of PV cases when JAK2 V617F is negative. 1, 4
• CALR and MPL mutation testing – these are not typical for PV but help exclude essential thrombocythemia if platelet count is also elevated. 1

Bone Marrow Biopsy Indications

Proceed to bone marrow biopsy if:

• JAK2 V617F or JAK2 exon 12 mutation is positive (to confirm hypercellularity with trilineage growth and pleomorphic megakaryocytes, which is a major WHO criterion). 1, 5
• Clinical suspicion remains high despite negative molecular testing, particularly if EPO is suppressed. 1

The biopsy typically shows hypercellularity for age with panmyelosis, prominent erythroid/granulocytic/megakaryocytic proliferation, pleomorphic mature megakaryocytes, and often depleted iron stores. 1, 5

Additional Molecular Testing Considerations

• In JAK2-positive patients, additional mutations (TET2, DNMT3A, ASXL1, SRSF2) are found in approximately 34.5% of cases and may have prognostic implications, though they are not required for diagnosis. 4
• Three percent of patients with erythrocytosis may have BCR-ABL1 fusion (chronic myeloid leukemia), which should be excluded if other features are atypical. 4

Management If PV Is Confirmed

Initiate the following therapies:

• Phlebotomy to maintain hemoglobin <14.0 g/dL in women (target hematocrit <45%), which reduces thrombotic risk. 5
• Aspirin 81 mg daily for thrombosis prophylaxis in JAK2-positive patients, even before hemoglobin reaches higher levels. 5
• Monitor for progression to myelofibrosis, as initial reticulin fibrosis is present in up to 20% of PV patients at diagnosis. 1

Critical Pitfalls to Avoid

• Do not dismiss this hemoglobin as "high normal" – 17.5 g/dL is 2 g/dL above the female upper limit and meets WHO major criteria for PV. 1, 2
• Do not assume iron deficiency excludes PV – iron deficiency may actually mask higher hemoglobin levels, and iron replacement can unmask the true degree of erythrocytosis. 5
• Do not order red cell mass measurement routinely – it adds cost without changing management in most cases and is only useful when hemoglobin is borderline and clinical features are ambiguous. 5
• Do not ignore suppressed EPO if hemoglobin is "only" 17.5 g/dL – a low EPO with elevated hemoglobin is physiologically inappropriate and highly specific for PV. 5