What is the best course of management for a 57-year-old post-menopausal female with erythrocytosis, presenting with elevated Hemoglobin (Hb) and Hematocrit (Hct) levels, and occasional increases in Red Blood Cells (RBCs)?

Management of Incidental Erythrocytosis in a 57-Year-Old Post-Menopausal Female

This patient requires immediate laboratory workup including JAK2 mutation testing, serum erythropoietin level, iron studies (ferritin and transferrin saturation), and peripheral blood smear to distinguish polycythemia vera from secondary causes—but therapeutic phlebotomy is NOT indicated at these levels (Hb 16.3 g/dL, Hct 47.6%) and should be avoided to prevent iron depletion and increased stroke risk. 1, 2, 3

Initial Diagnostic Approach

Confirm True Erythrocytosis

• Repeat hemoglobin and hematocrit measurements to confirm persistent elevation, as a single measurement is unreliable for establishing diagnosis 2, 4
• This patient's values (Hb 16.3 g/dL, Hct 47.6%, RBC 5.36) are elevated compared to normal post-menopausal female ranges (Hb 14.0 ± 2.0 g/dL, Hct 41 ± 5%) 2
• Ensure adequate hydration status before proceeding, as relative polycythemia from plasma volume depletion can mimic true erythrocytosis 2, 3

Essential Laboratory Workup

Order immediately: 2, 3

• Complete blood count with red cell indices to assess white blood cells and platelets (leukocytosis or thrombocytosis suggests polycythemia vera)
• JAK2 mutation testing (both exon 14 V617F and exon 12) - present in up to 97% of polycythemia vera cases 2, 4
• Serum erythropoietin (EPO) level - low or low-normal suggests primary polycythemia vera; elevated suggests secondary causes 3, 4
• Iron studies (serum ferritin and transferrin saturation) - iron deficiency can coexist with erythrocytosis and mask its full extent 2, 3
• Peripheral blood smear to evaluate red cell morphology 2, 3
• Reticulocyte count to assess bone marrow response 2

Diagnostic Algorithm Based on EPO Level

If EPO is Low or Low-Normal (Primary Erythrocytosis)

• JAK2 mutation positive: Diagnose polycythemia vera if WHO criteria met (elevated Hb/Hct AND JAK2 mutation plus one minor criterion) 2, 4
• Bone marrow biopsy required if JAK2 positive to confirm diagnosis and assess for trilineage myeloproliferation 2
• Refer immediately to hematology for confirmed polycythemia vera 2

If EPO is Normal or Elevated (Secondary Erythrocytosis)

Systematically evaluate for: 2, 3

• Hypoxic causes:

  • Sleep study for obstructive sleep apnea (nocturnal hypoxemia drives EPO production) 2
  • Pulmonary function tests and chest imaging for chronic obstructive pulmonary disease 2
  • Smoking history (carbon monoxide exposure causes "smoker's polycythemia") 2

• Non-hypoxic causes:

  • Renal imaging (ultrasound or CT) to exclude renal cell carcinoma, hydronephrosis, or cystic disease that produce EPO 2
  • Medication review for testosterone use (prescribed or unprescribed) 2
  • Screen for other EPO-producing tumors (hepatocellular carcinoma, pheochromocytoma, uterine leiomyoma) 2

Critical Management Principles

What NOT to Do

Avoid therapeutic phlebotomy at these levels. 1, 3, 5

• Phlebotomy is indicated ONLY when Hb >20 g/dL AND Hct >65% with symptoms of hyperviscosity (headache, visual disturbances, poor concentration) after excluding dehydration 1, 2, 3
• Repeated routine phlebotomies are contraindicated - they cause iron depletion, decreased oxygen-carrying capacity, and paradoxically INCREASE stroke risk 1, 3, 5
• Iron-deficient red blood cells have reduced deformability and are the strongest independent predictor for cerebrovascular events 5

What TO Do

For Secondary Erythrocytosis: 2, 3

• Treat the underlying condition (smoking cessation, CPAP for sleep apnea, manage COPD)
• Discontinue or reduce testosterone if causative
• Monitor hemoglobin and hematocrit periodically
• Maintain adequate hydration as first-line therapy 3

For Confirmed Polycythemia Vera: 2

• Maintain hematocrit strictly <45% through therapeutic phlebotomy to reduce thrombotic risk (CYTO-PV trial showed 2.7% vs 9.8% event rate, P=0.007)
• Initiate low-dose aspirin (81-100 mg daily) as second cornerstone of therapy for thrombosis prevention
• Hematology referral for cytoreductive therapy consideration if high-risk features present

Special Considerations for Iron Status

• If iron deficiency is confirmed (low ferritin or transferrin saturation), cautious oral iron supplementation with close hemoglobin monitoring is necessary 2, 3
• Iron deficiency should be corrected even in the presence of erythrocytosis, as it increases stroke risk 3, 5
• Warning: Oral iron can cause rapid and dramatic increases in red cell mass - monitor hemoglobin closely and discontinue once ferritin normalizes 1

Common Pitfalls to Avoid

• Never perform phlebotomy without meeting strict criteria (Hb >20 g/dL, Hct >65%, symptoms present, dehydration excluded) 1, 3
• Never assume low EPO automatically means polycythemia vera - up to 30% of PV patients may have normal or even elevated EPO levels 6
• Never overlook coexisting iron deficiency - it can mask the full extent of erythrocytosis while worsening hyperviscosity symptoms 3, 5
• Never use hematocrit alone for monitoring - hemoglobin is more reliable as hematocrit can falsely increase 2-4% with sample storage 2

Immediate Next Steps for This Patient

1. Order the complete laboratory panel described above (JAK2, EPO, iron studies, smear) 2, 3
2. Ensure adequate hydration and reassess in 1-2 weeks with repeat CBC 3
3. Take targeted history for symptoms of hyperviscosity, cardiopulmonary symptoms suggesting hypoxemia, smoking history, medication use (especially testosterone), and family history of erythrocytosis 2, 3
4. Do NOT perform phlebotomy at current levels - this would be harmful 1, 3, 5
5. Refer to hematology if JAK2 positive or if diagnosis remains unclear after initial workup 2