What can cause an increase in both hemoglobin (Hgb) and hematocrit (Hct)?

Causes of Elevated Hemoglobin and Hematocrit

Both hemoglobin and hematocrit increase together due to either an absolute increase in red blood cell mass (true polycythemia) or a decrease in plasma volume (relative polycythemia), with dehydration being the most common cause in clinical practice. 1

Primary Mechanisms

The elevation of both Hgb and Hct occurs through two fundamental pathways:

True (Absolute) Polycythemia

This represents an actual increase in red blood cell mass and can be further categorized:

Primary Polycythemia:

• Polycythemia vera (PV) - a clonal myeloproliferative disorder caused by JAK2 mutations, characterized by autonomous overproduction of red cells, often accompanied by elevated white cells and platelets 1, 2
• Erythropoietin receptor mutations causing unregulated red cell production 3
• High-oxygen-affinity hemoglobin variants that decrease oxygen delivery and trigger compensatory erythropoiesis 1

Secondary Polycythemia (Hypoxia-Driven):

• Chronic obstructive pulmonary disease (COPD) and other chronic lung diseases causing tissue hypoxia 1
• Obstructive sleep apnea producing nocturnal hypoxemia that drives erythropoietin production 1
• "Smoker's polycythemia" - the most frequent cause of increased hematocrit, resulting from chronic carbon monoxide exposure causing tissue hypoxia and stimulating erythropoietin production 1, 4
• Cyanotic congenital heart disease where erythrocytosis is a compensatory response to improve oxygen transport 1
• High altitude residence - physiological adaptation with specific increases based on elevation (e.g., +0.8 g/dL Hb at 2,000 meters, +3.5 g/dL at 4,000 meters) 1

Secondary Polycythemia (Hypoxia-Independent):

• Malignancies producing erythropoietin autonomously: renal cell carcinoma, hepatocellular carcinoma, pheochromocytoma, uterine leiomyoma, and meningioma 1
• Erythropoietin therapy - iatrogenic cause with expected Hgb rise of 0.3 g/dL per week (Hct rise of 1% per week) 5, 1

Relative (Apparent) Polycythemia

This represents decreased plasma volume with normal red cell mass:

• Dehydration - the most common cause of relative polycythemia 1, 6
• Diuretic use causing plasma volume depletion 1
• Burns with fluid shifts 1
• Stress polycythemia (Gaisböck syndrome) 1

Diagnostic Algorithm

Step 1: Confirm True Elevation

• Males: Hgb >18.5 g/dL or Hct >55% 1
• Females: Hgb >16.5 g/dL or Hct >49.5% 1
• Note: Males with Hct >60% and females with Hct >55% always have absolute polycythemia 4

Step 2: Assess for Relative vs. Absolute Polycythemia

• Evaluate hydration status clinically and recheck CBC after adequate hydration 1, 6
• If values normalize with hydration, diagnosis is relative polycythemia 6

Step 3: If True Polycythemia Confirmed

• Test for JAK2 mutations (both exon 14 and exon 12) to evaluate for polycythemia vera 1
• Measure serum erythropoietin levels: low/normal suggests PV, elevated suggests secondary causes 2, 7
• Obtain complete blood count with differential - elevated white cells and platelets suggest PV 4
• Check for splenomegaly - presence strongly suggests PV 4, 8

Step 4: Evaluate Secondary Causes

• Obtain detailed smoking history and assess for carbon monoxide exposure 1
• Consider sleep study if nocturnal hypoxemia suspected 1
• Evaluate for chronic lung disease 1
• Screen for malignancies if clinically indicated 1
• Review medication list for erythropoietin or testosterone use 1

Physiological Variations

Gender Differences:

• Adult males/post-menopausal females: Hgb 15.5 ± 2.0 g/dL, Hct 47 ± 6% 5
• Menstruating females: Hgb 14.0 ± 2.0 g/dL, Hct 41 ± 5% 5
• These differences emerge at puberty due to testosterone and estrogen effects 5

Critical Management Considerations

When to Intervene:

• Therapeutic phlebotomy is indicated ONLY when Hgb >20 g/dL and Hct >65% with symptoms of hyperviscosity 1, 9
• Target Hct <45% in polycythemia vera to reduce thrombotic risk 2
• Repeated routine phlebotomies are contraindicated due to risk of iron depletion, decreased oxygen-carrying capacity, and stroke 1

Common Pitfalls:

• Don't perform aggressive phlebotomy without adequate volume replacement - replace with equal volume of dextrose or saline 1
• Don't overlook coexisting iron deficiency - iron-deficient red cells have reduced oxygen-carrying capacity and deformability, increasing stroke risk 1
• Avoid allowing rapid increases in Hct (>8 percentage points per month) in patients on erythropoietin therapy - reduce dose by 25% if this occurs 5, 9

Laboratory Considerations:

• Hemoglobin is more accurate than hematocrit for monitoring because Hct can falsely increase by 2-4% with prolonged sample storage, while Hgb remains stable 5, 1
• Hyperglycemia falsely elevates MCV and calculated Hct but does not affect Hgb measurement 5