What is the appropriate management for a 52-year-old male with erythrocytosis, hyperhemoglobinemia, and hyperhematocrit?

Management of Erythrocytosis in a 52-Year-Old Male

This patient requires immediate JAK2 mutation testing to distinguish polycythemia vera from secondary causes, followed by a systematic evaluation for secondary erythrocytosis if JAK2 is negative. 1, 2, 3

Initial Diagnostic Approach

Confirm True Erythrocytosis

• Repeat hemoglobin and hematocrit measurements to confirm persistent elevation, as single measurements are unreliable for establishing diagnosis 1, 2
• This patient's values (Hgb 18.0 g/dL, Hct 53.2%) exceed diagnostic thresholds for erythrocytosis in men (Hgb >18.5 g/dL or Hct >55%) but are borderline and warrant confirmation 1, 3
• Ensure adequate hydration status before interpreting results, as relative polycythemia from dehydration can falsely elevate these values 1, 2

Essential Laboratory Workup

Order the following tests immediately:

• JAK2 mutation testing (both exon 14 V617F and exon 12) - present in >95% of polycythemia vera cases 1, 3
• Serum ferritin and transferrin saturation - iron deficiency can coexist with erythrocytosis and mask its full extent 1, 2
• Serum erythropoietin (EPO) level - low/normal suggests primary polycythemia vera, elevated suggests secondary causes 2, 4
• Reticulocyte count to assess bone marrow response 1
• Peripheral blood smear to evaluate red cell morphology 1, 2
• C-reactive protein (CRP) to assess for inflammatory conditions 1

Diagnostic Algorithm Based on Results

If JAK2 Mutation is Positive

• Refer immediately to hematology for bone marrow biopsy to confirm polycythemia vera diagnosis 1, 3
• Bone marrow biopsy is required to assess for trilineage myeloproliferation and meet WHO diagnostic criteria 1, 3
• WHO criteria require: elevated Hgb/Hct AND JAK2 mutation PLUS one minor criterion (bone marrow hypercellularity, subnormal EPO, or endogenous erythroid colonies) 1

If JAK2 Mutation is Negative

Systematically evaluate for secondary causes:

Hypoxic causes:

• Sleep study for obstructive sleep apnea - nocturnal hypoxemia drives EPO production 1, 2
• Pulmonary function tests and chest imaging for chronic obstructive pulmonary disease 1, 2
• Smoking history assessment - carbon monoxide exposure causes "smoker's polycythemia" which resolves with cessation 1, 2

Non-hypoxic causes:

• Renal imaging (ultrasound or CT) to exclude renal cell carcinoma, hydronephrosis, or cystic disease that produce EPO 1, 2
• Medication review - particularly testosterone use (prescribed or unprescribed) which commonly causes erythrocytosis 1, 2
• Consider imaging for other EPO-producing tumors (hepatocellular carcinoma, pheochromocytoma, uterine leiomyoma, meningioma) if clinically indicated 1

Management Strategy

Current Management - DO NOT Phlebotomize Yet

This patient does NOT meet criteria for therapeutic phlebotomy at present:

• Phlebotomy is indicated ONLY when Hgb >20 g/dL AND Hct >65% with symptoms of hyperviscosity, after excluding dehydration 1, 2
• This patient's Hct of 53.2% is well below the 65% threshold 1, 2
• Repeated routine phlebotomies are explicitly contraindicated as they cause iron depletion, decreased oxygen-carrying capacity, and paradoxically increase stroke risk 1, 2

Immediate Actions

• Ensure adequate hydration as first-line therapy 2
• Assess for symptoms of hyperviscosity (headache, visual disturbances, fatigue, poor concentration) 2
• Monitor iron status closely - if transferrin saturation <20%, iron deficiency is present and requires cautious supplementation with close Hgb monitoring 1, 2

If Polycythemia Vera is Confirmed

• Maintain hematocrit strictly <45% through therapeutic phlebotomy to reduce thrombotic risk - this is the strongest evidence-based target from the CYTO-PV trial 1, 3
• Initiate low-dose aspirin (81-100 mg daily) as second cornerstone of therapy for thrombosis prevention (unless contraindicated) 1, 3
• Consider cytoreductive therapy (hydroxyurea or interferon) if patient is age ≥60 years, has prior thrombosis, or has persistent symptoms 3

If Secondary Erythrocytosis is Confirmed

• Treat the underlying condition - this is the primary management strategy 1, 2
• Smoking cessation for smoker's polycythemia 1, 2
• CPAP therapy for obstructive sleep apnea 1, 2
• Management of COPD or other pulmonary disease 1, 2
• Dose adjustment or discontinuation of testosterone if causative 1, 2
• Target Hct 55-60% may be appropriate in secondary erythrocytosis as the elevated Hct serves a compensatory physiological role 1

Critical Pitfalls to Avoid

• Never perform aggressive phlebotomy without adequate volume replacement - this increases hemoconcentration and stroke risk 1, 2
• Do not overlook coexisting iron deficiency - iron-deficient red cells have reduced oxygen-carrying capacity and deformability, increasing stroke risk even with elevated Hct 1, 2
• Do not use standard PV diagnostic thresholds without considering physiological variations - altitude, age, and sex affect normal Hgb/Hct ranges 1
• Do not assume elevated Hct alone determines thrombotic risk - other cellular changes in polycythemia affect thrombosis independent of Hct 5
• Do not miss masked polycythemia vera - rare cases present with normal Hgb/Hct due to blood dilution or coincidental blood loss but still have JAK2 mutations and thrombotic risk 6

Monitoring Plan

• Repeat CBC every 3 months during evaluation and management 2
• Monitor renal function as chronic erythrocytosis can affect glomerular filtration 2
• Serial measurements are appropriate for borderline cases to establish trend 1