What is the appropriate management and diagnosis for a female patient with elevated Red Blood Cell (RBC) count, hyperferritinemia, elevated Hematocrit (Hct), elevated Hemoglobin (Hgb), and abnormal Mean Corpuscular Hemoglobin (MCH), with otherwise normal laboratory results?

Evaluation of Elevated RBC Count with Borderline Ferritin in a Young Female

This patient has borderline elevated RBC count (5.49) with elevated MCH (26.5), normal hemoglobin (14.5 g/dL), normal hematocrit (44%), and low-normal ferritin (51 ng/mL), which most likely represents early iron deficiency coexisting with a compensatory erythrocytosis or a physiological variant rather than polycythemia vera or secondary polycythemia. 1

Initial Diagnostic Assessment

The hemoglobin (14.5 g/dL) and hematocrit (44%) are within normal range for females (normal post-menopausal: Hb 14.0 ± 2.0 g/dL, Hct 41 ± 5%), though the RBC count of 5.49 is mildly elevated. 1 The elevated MCH of 26.5 pg is unusual and warrants further investigation, as this typically suggests macrocytic cells, yet the overall picture doesn't indicate true polycythemia. 2

Key Laboratory Findings to Interpret

• Ferritin of 51 ng/mL is borderline low for a female and may indicate depleting iron stores, particularly if there are ongoing losses. 2 In non-dialysis females, ferritin <11 ng/mL predicts insufficient iron stores, but levels between 11-100 ng/mL represent a gray zone. 2

• The combination of elevated RBC count with borderline ferritin suggests possible iron deficiency coexisting with erythrocytosis, creating a "microcytic polycythemia" pattern. 3 This occurs when iron deficiency limits hemoglobin synthesis while erythropoietin drive remains elevated. 3

• Hemoglobin is more reliable than hematocrit for assessment because hematocrit can falsely increase by 2-4% with sample storage, while hemoglobin remains stable. 2, 1

Recommended Diagnostic Workup

Complete the Iron Panel

Order transferrin saturation (TSAT) immediately to assess functional iron availability for erythropoiesis, as this is less affected by inflammation than ferritin and correlates better with hemoglobin levels. 2 A TSAT <20% would confirm functional iron deficiency. 2

Obtain C-reactive protein (CRP) to determine if the ferritin level is falsely elevated by inflammation, as ferritin is an acute-phase reactant. 2, 1

Assess for Secondary Causes

Evaluate for occult blood loss, particularly gastrointestinal bleeding, as iron deficiency in a female without obvious menstrual losses should prompt careful GI assessment. 2 This is critical given the borderline ferritin.

Screen for hypoxic causes if RBC elevation persists:

• Sleep study for obstructive sleep apnea if symptoms of snoring, daytime fatigue, or witnessed apneas exist 1
• Smoking history and carbon monoxide exposure assessment 1
• Pulse oximetry at rest for at least 5 minutes to document baseline oxygen saturation 2

Review medication history for testosterone use (prescribed or unprescribed), which can cause erythrocytosis in young adults. 1

Rule Out Polycythemia Vera (Low Probability)

JAK2 mutation testing is NOT indicated at this time because the hemoglobin (14.5 g/dL) and hematocrit (44%) do not meet diagnostic thresholds for polycythemia vera in females (Hb >16.5 g/dL, Hct >48-49%). 2, 1 The WHO criteria require elevated hemoglobin/hematocrit as a major criterion. 2, 1

Management Approach

Iron Supplementation Strategy

If TSAT confirms <20%, initiate oral iron supplementation (ferrous sulfate 325 mg daily or equivalent) with close monitoring of hemoglobin levels. 1 In the context of borderline erythrocytosis, cautious iron supplementation with hemoglobin monitoring every 4-6 weeks is necessary to avoid rapid increases in red cell mass. 1

Monitor for rapid hemoglobin rise, as increases >0.3 g/dL per week or hematocrit rises >8 percentage points per month warrant dose reduction. 1

Phlebotomy is NOT Indicated

Therapeutic phlebotomy is explicitly contraindicated at these levels, as it is only indicated when hemoglobin exceeds 20 g/dL and hematocrit exceeds 65% with hyperviscosity symptoms. 1 At current levels (Hb 14.5, Hct 44%), phlebotomy would cause iron depletion, decreased oxygen-carrying capacity, and paradoxically increase stroke risk. 2, 1

Follow-Up Monitoring

Repeat complete blood count with iron studies in 3 months to assess response to iron supplementation (if initiated) and document stability or progression of RBC elevation. 1 If RBC count continues to rise despite iron repletion, reassess for secondary causes.

Serial measurements are more reliable than single values for establishing a diagnosis, particularly with borderline findings. 1

Common Pitfalls to Avoid

Do not diagnose polycythemia vera based on elevated RBC count alone when hemoglobin and hematocrit are normal, as RBC count can be elevated in iron deficiency states where smaller cells require higher numbers to maintain normal hemoglobin. 3, 4

Do not overlook coexisting iron deficiency in erythrocytosis, as iron-deficient red blood cells have reduced oxygen-carrying capacity and deformability, increasing stroke risk even with elevated RBC counts. 2, 1, 3

Do not perform aggressive phlebotomy without adequate volume replacement or in the absence of true polycythemia, as this increases hemoconcentration and thrombotic risk. 1

Mean corpuscular volume (MCV) is unreliable for screening iron deficiency in erythrocytosis, and serum ferritin, transferrin saturation, and iron levels are required for accurate diagnosis. 1