In a 51-year-old woman with hemoglobin 16.6 g/dL, hematocrit 50.6 % and mean corpuscular volume 99 fL, what is the most likely diagnosis and recommended first‑line management?

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Polycythemia Vera (PV)

This 51-year-old woman meets diagnostic criteria for polycythemia vera based on her elevated hemoglobin (16.6 g/dL, exceeding the 16.0 g/dL threshold for women) and hematocrit (50.6%, exceeding the 48% threshold for women), and first-line management requires JAK2 mutation testing followed by bone marrow biopsy to confirm the diagnosis, then risk-stratified therapy with phlebotomy and low-dose aspirin. 1

Diagnostic Criteria

The 2016 WHO diagnostic criteria for polycythemia vera require meeting either all 3 major criteria or the first 2 major criteria plus the minor criterion: 1

Major criteria:

  • Hemoglobin >16.0 g/dL in women (this patient has 16.6 g/dL) OR hematocrit >48% in women (this patient has 50.6%) OR increased red cell mass 1
  • Bone marrow biopsy showing hypercellularity for age with trilineage growth (panmyelosis) including prominent erythroid, granulocytic, and megakaryocytic proliferation with pleomorphic, mature megakaryocytes 1
  • Presence of JAK2 V617F or JAK2 exon 12 mutation 1

Minor criterion:

  • Subnormal serum erythropoietin (EPO) level 1

Essential Diagnostic Workup

Order the following tests immediately to establish the diagnosis: 1

  • JAK2 V617F mutation testing – present in approximately 95% of PV cases and confirms clonal myeloproliferation 1
  • Serum erythropoietin level – typically suppressed in PV (serves as the minor criterion) 1
  • Bone marrow biopsy with reticulin staining – demonstrates hypercellularity with trilineage growth and pleomorphic megakaryocytes; initial myelofibrosis is present in up to 20% of patients and predicts more rapid progression to post-PV myelofibrosis 1

If JAK2 V617F is negative, test for JAK2 exon 12 mutations, which account for most remaining PV cases. 1

Clinical Context and Pitfalls

The normal MCV of 99 fL does not exclude PV – polycythemia vera typically presents with normocytic red cells unless concurrent iron deficiency is present (which can mask the elevated hemoglobin). 1

A bone marrow biopsy may not be required if sustained absolute erythrocytosis is present (hemoglobin >16.5 g/dL in women, hematocrit >49%) and both the JAK2 mutation and subnormal EPO level are confirmed. However, performing the biopsy is still recommended because it detects initial myelofibrosis, which occurs in up to 20% of patients and predicts faster progression to post-PV myelofibrosis. 1

Risk Stratification and First-Line Management

Once PV is confirmed, assess thrombotic risk based on age and prior thrombosis history: 1

  • Low risk: Age <60 years AND no prior thrombosis
  • High risk: Age ≥60 years OR prior thrombosis

All patients require: 1

  • Phlebotomy to maintain hematocrit <45% in all patients (reduces thrombotic risk)
  • Low-dose aspirin (81–100 mg daily) unless contraindicated
  • Cardiovascular risk factor modification (control hypertension, diabetes, hyperlipidemia)

High-risk patients also require cytoreductive therapy with hydroxyurea as first-line agent. 1

Symptom Assessment

Use the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) at baseline to quantify symptom burden (fatigue, pruritus after bathing, night sweats, bone pain, abdominal discomfort from splenomegaly). 1

Monitor symptom status during treatment; worsening symptoms may signal disease progression and warrant re-evaluation. 1

Alternative Diagnoses to Exclude

Before confirming PV, rule out secondary causes of erythrocytosis: 1

  • Hypoxia-driven erythrocytosis (chronic lung disease, sleep apnea, high altitude, smoking, carbon monoxide exposure) – EPO will be elevated, not suppressed
  • Renal causes (renal artery stenosis, polycystic kidney disease, renal cell carcinoma) – EPO inappropriately normal or elevated
  • Other tumors secreting EPO (hepatocellular carcinoma, cerebellar hemangioblastoma, uterine leiomyoma)

The combination of elevated hemoglobin/hematocrit with suppressed EPO and positive JAK2 mutation distinguishes primary PV from all secondary causes. 1

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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