What is the appropriate management for a patient with a mildly elevated Red Blood Cell (RBC) count, normal White Blood Cell (WBC) and Platelet counts, and a history of past RBC elevations?

Evaluation and Management of Mild Erythrocytosis with Stable Hemoglobin/Hematocrit

This patient requires confirmation of true erythrocytosis through repeat testing and systematic evaluation for secondary causes before considering any intervention, as the mildly elevated RBC count with normal hemoglobin and hematocrit does not meet criteria for therapeutic intervention and may represent a spurious result or benign secondary cause. 1

Immediate Diagnostic Confirmation

Repeat the complete blood count within 2-4 weeks to confirm persistence of the elevated RBC count, as spurious elevations can occur from technical factors including sample storage, high white blood cell counts, or analyzer-specific issues 2. The stability of your patient's hemoglobin (16.3 g/dL) and hematocrit (47.6%) over time, despite past RBC elevations, suggests this may not represent true pathologic erythrocytosis 1.

Key Laboratory Assessment

Order the following tests to establish the diagnosis and identify underlying causes:

• Peripheral blood smear review to evaluate RBC morphology, assess for microcytosis (suggesting iron deficiency), and rule out spurious counts from WBC interference 1, 3
• Iron studies including serum ferritin and transferrin saturation, as iron deficiency commonly causes elevated RBC counts with relatively normal or low hemoglobin—creating microcytic polycythemia 4, 1
• Reticulocyte count to assess bone marrow erythropoietic activity 1
• Serum erythropoietin level to differentiate primary from secondary causes 1

Diagnostic Thresholds and Clinical Context

This patient does NOT meet diagnostic criteria for polycythemia vera or pathologic erythrocytosis requiring intervention. Diagnostic thresholds are hemoglobin >18.5 g/dL in men (>16.5 g/dL in women) or hematocrit >55% in men (>49.5% in women) 1. Your patient's values of hemoglobin 16.3 g/dL and hematocrit 47.6% fall well below these thresholds.

Common Pitfall to Avoid

Do not pursue JAK2 mutation testing or hematology referral at this stage, as the patient's hemoglobin and hematocrit are within normal range despite the elevated RBC count 1. This pattern often indicates:

• Iron deficiency causing increased RBC production with smaller, less hemoglobin-containing cells 4, 1
• Spurious RBC count from analyzer interference 2
• Dehydration causing hemoconcentration 4

Systematic Evaluation for Secondary Causes

Obtain detailed history focusing on:

• Smoking history and carbon monoxide exposure, as "smoker's polycythemia" produces erythropoietin-driven erythrocytosis that resolves with cessation 1
• Sleep patterns and daytime somnolence to screen for obstructive sleep apnea causing nocturnal hypoxemia 1
• Testosterone use (prescribed or unprescribed), which commonly causes erythrocytosis 1
• Chronic lung disease symptoms suggesting hypoxemia-driven erythropoietin production 1

Management Algorithm Based on Findings

If Iron Deficiency is Confirmed (Ferritin Low, Microcytic Cells)

Initiate cautious oral iron supplementation with weekly hemoglobin monitoring, as iron replacement frequently causes rapid, dramatic increases in red cell mass 4. Discontinue supplementation once ferritin and transferrin saturation normalize 4. If oral iron is not tolerated, use pulses of intravenous iron instead 4.

If Secondary Cause is Identified

Address the underlying condition (smoking cessation, CPAP for sleep apnea, discontinue testosterone) rather than treating the RBC elevation directly 1.

If No Cause is Found and Values Remain Stable

Continue monitoring with repeat CBC every 3-6 months, watching specifically for progression of hemoglobin above 18.5 g/dL or hematocrit above 55% in men (16.5 g/dL or 49.5% in women) 1. Only pursue JAK2 testing and hematology referral if these thresholds are crossed 1.

Critical Contraindications

Therapeutic phlebotomy is absolutely contraindicated in this patient. Phlebotomy should only be performed when hemoglobin exceeds 20 g/dL AND hematocrit exceeds 65%, accompanied by hyperviscosity symptoms, and only after confirming adequate hydration and iron stores 4. Repeated routine phlebotomies risk iron depletion, which creates rigid microcytic red cells that are the strongest independent predictor of cerebrovascular events 4.

Monitoring Strategy

Use hemoglobin rather than hematocrit for ongoing monitoring, as hemoglobin remains stable during sample storage while hematocrit can falsely increase by 2-4% 1. The RBC count alone should not drive clinical decisions when hemoglobin and hematocrit remain normal 3, 5.