What is the significance of elevated red blood cell (RBC) count, hematocrit (Hct), and hemoglobin (Hgb) in a 44-year-old female with normal comprehensive metabolic panel (CMP) and ferritin levels?

Elevated RBC Count and Hematocrit in a 44-Year-Old Female

This pattern of mildly elevated RBC (5.12), hematocrit (47.3%), and hemoglobin (15.3 g/dL) with low-normal ferritin (30 ng/mL) most likely represents relative polycythemia from plasma volume contraction (dehydration, diuretic use) or early iron deficiency with hemoconcentration, rather than true polycythemia or iron overload. 1

Understanding the Laboratory Pattern

Your patient's values show:

• RBC 5.12 (mildly elevated for a menstruating female)
• Hematocrit 47.3% (above the normal range of 41 ± 5% for menstruating females) 2
• Hemoglobin 15.3 g/dL (within normal range of 14.0 ± 2.0 g/dL for menstruating females) 2
• Ferritin 30 ng/mL (low-normal, concerning for depleted iron stores in a menstruating female) 2

The key insight is that the hematocrit is disproportionately elevated compared to the hemoglobin. This discordance suggests either laboratory artifact from sample storage (which falsely elevates hematocrit by 2-4% while hemoglobin remains stable) or true hemoconcentration from volume contraction. 2

Most Likely Explanations

1. Relative Polycythemia (Hemoconcentration)

The most common cause of this pattern is plasma volume contraction, not true increase in red cell mass. 1 Look for:

• Dehydration (inadequate fluid intake, excessive sweating, diarrhea)
• Diuretic use (thiazides, loop diuretics)
• Smoking (causes chronic plasma volume contraction)
• Hypertension (associated with reduced plasma volume)
• Obesity (Gaisböck syndrome - stress polycythemia) 1

2. Early Iron Deficiency with Compensatory Erythrocytosis

Ferritin of 30 ng/mL is concerning for depleted iron stores in a menstruating female, where iron deficiency prevalence ranges from 15-35%. 2 The pattern suggests:

• Iron stores are borderline depleted (ferritin <50 ng/mL indicates risk) 2
• The bone marrow is compensating by producing more RBCs, but each cell has less hemoglobin
• This creates elevated RBC count with relatively normal hemoglobin 2

Check transferrin saturation immediately - if TSAT <20% with ferritin <50 ng/mL, this confirms functional or absolute iron deficiency despite the elevated hematocrit. 1

3. Laboratory Artifact

Hematocrit is calculated from RBC count and mean corpuscular volume (MCV), making it susceptible to pre-analytical errors. 2 Specifically:

• Blood sample storage >24 hours causes MCV to increase by 2-4%, falsely elevating calculated hematocrit 2
• Hemoglobin measurement remains stable under the same conditions 2
• Hemoglobin is the more accurate measure - your patient's hemoglobin of 15.3 g/dL is actually normal for a menstruating female 2

What This Pattern Does NOT Represent

Not Hereditary Hemochromatosis

Ferritin of 30 ng/mL essentially rules out iron overload. 1 In hereditary hemochromatosis:

• Ferritin is typically >300 ng/mL and often >1000 ng/mL 1
• Transferrin saturation is ≥45% 1
• Your patient's low-normal ferritin excludes this diagnosis 1

While one small study suggested elevated hemoglobin/hematocrit in HFE mutations (median Hct 44.9-48% in various genotypes), this occurred in the context of markedly elevated ferritin levels requiring phlebotomy. 3 Your patient's ferritin of 30 ng/mL makes this irrelevant.

Not Polycythemia Vera

True polycythemia vera would show: 1

• Hemoglobin >16.5 g/dL in women (your patient is 15.3 g/dL)
• Elevated ferritin (iron stores are typically replete or elevated)
• JAK2 mutation positivity
• Aquagenic pruritus, splenomegaly 1

Diagnostic Algorithm

Step 1: Repeat CBC with Hemoglobin Focus

• Order a fresh morning sample, processed within 4 hours 2
• Focus on hemoglobin (more reliable than hematocrit) 2
• If hemoglobin remains normal (14-16 g/dL) but hematocrit elevated, this confirms relative polycythemia 2

Step 2: Assess Iron Status Properly

Order fasting transferrin saturation alongside repeat ferritin - this is the single most important test to distinguish true iron status from inflammatory causes. 1 Interpretation:

• If TSAT <20% with ferritin 30 ng/mL: Confirms iron deficiency despite normal hemoglobin 1
• If TSAT ≥20%: Iron stores are adequate; elevated RBC/Hct represents relative polycythemia 1

Step 3: Evaluate for Secondary Causes

If relative polycythemia is confirmed (normal hemoglobin, elevated hematocrit, normal TSAT): 1

• Assess hydration status and recent fluid intake
• Review medications (diuretics, testosterone, erythropoietin)
• Smoking history (causes chronic hemoconcentration)
• Check for sleep apnea symptoms (snoring, daytime somnolence, witnessed apneas)
• Consider chronic hypoxia (pulse oximetry, pulmonary function tests if indicated) 1

Step 4: Consider Metabolic Syndrome

Elevated hematocrit with low-normal ferritin can occur in metabolic syndrome, where ferritin reflects hepatocellular injury rather than iron stores. 1 Assess for:

• Obesity (BMI >30)
• Hypertension
• Dyslipidemia
• Insulin resistance/diabetes 1

One study found mean ferritin 163 ng/mL in metabolic syndrome patients (higher than your patient), but hemoglobin concentrations were not significantly different from controls, suggesting metabolic syndrome does not cause true polycythemia. 4

Management Recommendations

If Iron Deficiency is Confirmed (TSAT <20%)

Initiate oral ferrous sulfate 300 mg three times daily immediately to replenish depleted iron stores, with a target ferritin >100 ng/mL and TSAT >20%. 1

• Continue supplementation for at least 3 months to fully replenish stores 1
• Recheck ferritin and TSAT after 3 months 1
• Investigate the source of iron loss - in a 44-year-old female, assess menstrual blood loss (heavy periods requiring pad changes every 1-2 hours suggest menorrhagia requiring gynecologic evaluation) 1

If Relative Polycythemia is Confirmed (Normal TSAT)

Address the underlying cause rather than the elevated hematocrit: 1

• Optimize hydration (target 2-3 liters daily)
• Discontinue or adjust diuretics if possible
• Smoking cessation counseling
• Weight loss if obese (target BMI <30)
• Treat sleep apnea if present (CPAP therapy) 1

Critical Pitfalls to Avoid

1. Do not use hematocrit alone to diagnose polycythemia - hemoglobin is more reliable and less affected by pre-analytical variables 2

2. Do not assume iron overload based on elevated RBC/Hct - ferritin of 30 ng/mL excludes this diagnosis 1

3. Do not overlook iron deficiency in menstruating females with ferritin <50 ng/mL - this represents depleted stores even if hemoglobin is normal 2

4. Do not order HFE genetic testing without first checking transferrin saturation - over 90% of elevated ferritin cases are not due to iron overload, and your patient has LOW ferritin 1

5. Do not supplement iron when TSAT is normal and ferritin >30 ng/mL without confirming deficiency - this represents adequate iron stores 1