What is the appropriate management for a patient with elevated Red Blood Cell (RBC) count, Hemoglobin (HGB), and Hematocrit (HCT)?

Management of Mildly Elevated RBC, Hemoglobin, and Hematocrit

Your patient has borderline erythrocytosis that requires confirmation with repeat testing and systematic evaluation for secondary causes before considering any intervention, as therapeutic phlebotomy is NOT indicated at these levels and could cause harm. 1

Initial Assessment and Confirmation

Repeat the complete blood count within 2-4 weeks to confirm persistent elevation, as a single measurement is unreliable for establishing a diagnosis. 1 Your patient's values (RBC 5.45, Hgb 16.0 g/dL, Hct 47.9%) are only marginally elevated and may represent normal variation or relative polycythemia from dehydration. 1

The diagnostic thresholds for true erythrocytosis requiring workup are:

• Hemoglobin >16.5 g/dL in women (your patient is at 16.0 g/dL)
• Hematocrit >49.5% in women (your patient is at 47.9%) 1

Your patient falls just below these thresholds, making this likely a borderline or incidental finding. 1

Comprehensive Laboratory Workup

If repeat testing confirms persistent elevation, order the following tests immediately:

• Serum ferritin and transferrin saturation to evaluate iron status, as iron deficiency can coexist with erythrocytosis and requires different management 1
• Reticulocyte count to assess bone marrow response 1
• C-reactive protein (CRP) to screen for inflammatory conditions 1
• Peripheral blood smear review to identify morphological abnormalities 1

The normal RDW (13.9%) and MCV (87.8 fL) make iron deficiency less likely but do not exclude it, as MCV is unreliable for screening iron deficiency in erythrocytosis. 1

Evaluation for Secondary Causes

Before considering polycythemia vera, systematically exclude secondary causes, which are far more common:

Hypoxic Causes

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

Non-Hypoxic Causes

• Medication review for testosterone use (prescribed or unprescribed), which commonly causes erythrocytosis in adults 1
• Renal imaging (ultrasound or CT) to exclude renal cell carcinoma, hydronephrosis, or cystic disease that can produce erythropoietin 1

Testing for Polycythemia Vera

Only proceed with JAK2 mutation testing if:

• Repeat testing confirms hemoglobin >16.5 g/dL or hematocrit >49.5% 1
• Secondary causes have been excluded 1
• Patient has PV-related features such as thrombocytosis, leukocytosis, splenomegaly, aquagenic pruritus, or unusual thrombosis 1

The JAK2 mutation is present in up to 97% of polycythemia vera cases. 1 If positive, bone marrow biopsy is required to confirm diagnosis and assess for trilineage myeloproliferation. 1

Critical Management Principles

Therapeutic phlebotomy is absolutely contraindicated at your patient's current levels. 1 The evidence-based thresholds for phlebotomy are:

• Hemoglobin >20 g/dL AND hematocrit >65% with symptoms of hyperviscosity 1
• Your patient's values (Hgb 16.0 g/dL, Hct 47.9%) are nowhere near these thresholds

Repeated routine phlebotomies cause iron depletion, decreased oxygen-carrying capacity, and paradoxically increase stroke risk. 1 This is a class III recommendation (contraindicated) from the American College of Cardiology. 1

Common Pitfalls to Avoid

• Never perform phlebotomy based on mildly elevated values alone, as this causes more harm than benefit through iron depletion 1
• Don't overlook dehydration as a cause of relative polycythemia, which requires rehydration rather than phlebotomy 1
• Don't use standard diagnostic thresholds if the patient lives at high altitude, as physiologic adaptation can increase hemoglobin by 0.2-4.5 g/dL depending on elevation 1
• Don't assume normal MCV excludes iron deficiency in erythrocytosis, as MCV is unreliable in this context 1

When to Refer to Hematology

Immediate hematology referral is indicated if:

• JAK2 mutation is positive 1
• Hemoglobin >20 g/dL with symptoms of hyperviscosity 1
• Unexplained splenomegaly 1
• Diagnosis remains unclear after initial workup 1

Specific Management Based on Etiology

If a secondary cause is identified:

• Smoking cessation for smoker's polycythemia 1
• CPAP therapy for obstructive sleep apnea 1
• Testosterone dose adjustment or discontinuation if causative 1
• Management of underlying pulmonary disease 1

If polycythemia vera is confirmed, maintain hematocrit strictly below 45% through phlebotomy to reduce thrombotic risk, and initiate low-dose aspirin (81-100 mg daily) as the second cornerstone of therapy. 1 This recommendation is based on the CYTO-PV trial showing significant reduction in thrombotic events (2.7% vs 9.8%, P=0.007). 1