What is the significance and recommended management of an asymptomatic 58-year-old woman with elevated red blood cell count, hemoglobin, and hematocrit?

Evaluation of Elevated RBC, Hemoglobin, and Hematocrit in a 58-Year-Old Woman

These values (RBC 5.35, hemoglobin 16.1 g/dL, hematocrit 48%) represent mild erythrocytosis that warrants systematic evaluation but does not require immediate therapeutic intervention such as phlebotomy. 1

Initial Assessment and Significance

Your patient's values exceed the WHO diagnostic threshold for polycythemia vera in women (hemoglobin >16.5 g/dL or hematocrit >48%), though only marginally. 2, 1 Specifically:

• Hemoglobin 16.1 g/dL is below the 16.5 g/dL threshold
• Hematocrit 48% meets the threshold exactly
• RBC 5.35 is elevated above typical female ranges

The 95th percentile for hemoglobin in post-menopausal women is approximately 15.2-15.6 g/dL, making this a statistically significant elevation. 1 However, these borderline values require confirmation with repeat testing before pursuing extensive workup, as a single measurement is unreliable. 1

Recommended Diagnostic Algorithm

Step 1: Confirm True Erythrocytosis

• Repeat hemoglobin and hematocrit within 2-4 weeks to confirm persistent elevation rather than transient changes 1
• Assess hydration status clinically, as dehydration is the most common cause of apparent erythrocytosis and must be excluded before extensive workup 3

Step 2: Initial Laboratory Panel

Order the following tests immediately: 1

• Complete blood count with differential to evaluate for thrombocytosis or leukocytosis suggesting myeloproliferative disorder
• Serum ferritin and transferrin saturation to assess iron status (iron deficiency can coexist with erythrocytosis, causing microcytic polycythemia) 1
• C-reactive protein (CRP) to identify inflammatory conditions 1
• Reticulocyte count to evaluate bone marrow response 1
• Peripheral blood smear to assess red cell morphology 1

Step 3: JAK2 Mutation Testing

If repeat testing confirms persistent elevation, order JAK2 mutation analysis (both exon 14 V617F and exon 12) as the cornerstone first-line test. 1, 3 This detects mutations in up to 97% of polycythemia vera cases and is essential for distinguishing primary from secondary erythrocytosis. 1

Step 4: Evaluate Secondary Causes (if JAK2 negative)

Hypoxia-driven causes: 1, 3

• Sleep study if nocturnal hypoxemia suspected (obesity, snoring, daytime fatigue)
• Pulmonary function tests and chest imaging for chronic lung disease
• Arterial oxygen saturation measurement

Non-hypoxia-driven causes: 1, 3

• Smoking history assessment (carbon monoxide exposure stimulates erythropoietin)
• Medication review for testosterone or erythropoietin therapy
• Renal imaging (ultrasound or CT) to exclude renal cell carcinoma or cystic disease producing erythropoietin
• Serum erythropoietin level (low/normal suggests polycythemia vera; elevated suggests secondary cause) 1

Management Based on Diagnosis

If Polycythemia Vera Confirmed (JAK2 positive + WHO criteria met)

Maintain hematocrit strictly below 45% through therapeutic phlebotomy to reduce thrombotic risk, based on the CYTO-PV trial showing 2.7% vs 9.8% event rate (P=0.007). 1, 3 A slightly lower target of approximately 42% is reasonable for women. 1

Initiate low-dose aspirin (81-100 mg daily) as the second cornerstone of therapy for thrombosis prevention. 1, 3

Refer to hematology for bone marrow biopsy confirmation and ongoing management. 1

If Secondary Erythrocytosis Identified

Treat the underlying condition: 1, 3

• CPAP therapy for obstructive sleep apnea
• Smoking cessation for smoker's polycythemia (typically resolves with cessation)
• Management of chronic lung disease
• Dose adjustment or discontinuation of testosterone if causative

Phlebotomy is contraindicated in secondary erythrocytosis except in rare circumstances when hemoglobin >20 g/dL and hematocrit >65% with documented hyperviscosity symptoms after excluding dehydration. 1, 3 Routine phlebotomy causes iron depletion, decreased oxygen-carrying capacity, and paradoxically increases stroke risk. 1

If Borderline/Observation Category

For values that remain borderline (hematocrit <52% in women) without meeting full diagnostic criteria: 1

• Serial monitoring every 6-12 months with hemoglobin/hematocrit measurements
• Avoid routine phlebotomy, which can cause iatrogenic harm
• Maintain iron sufficiency, as iron deficiency is the strongest independent predictor of cerebrovascular events in erythrocytosis 1

Critical Pitfalls to Avoid

Never perform phlebotomy at these hemoglobin/hematocrit levels. 1, 3 Therapeutic phlebotomy is indicated only when hemoglobin >20 g/dL and hematocrit >65% with hyperviscosity symptoms, after excluding dehydration. 1

Do not overlook coexisting iron deficiency. 1 Iron deficiency frequently coexists with erythrocytosis and requires opposite management (iron supplementation rather than phlebotomy). Mean corpuscular volume (MCV) is unreliable for screening iron deficiency in erythrocytosis; serum ferritin and transferrin saturation are required. 1

Do not dismiss borderline elevations. 3 A sustained increase of ≥2 g/dL from baseline hemoglobin should raise suspicion for early polycythemia vera, even without reaching absolute diagnostic thresholds. 3

If phlebotomy is ever performed, replace removed blood volume with equal fluid to prevent hemoconcentration and reduce stroke risk. 1