What is hematocrit, how is it measured, what are the normal reference ranges, and what is its clinical significance?

What is Hematocrit?

Hematocrit is the percentage of blood volume occupied by red blood cells, measured either by centrifugation or automated cell counters, with normal ranges of 42–54% in men and 38–46% in women at sea level. 1

Definition and Measurement

Hematocrit represents the proportion of whole blood that consists of packed red blood cells after separation from plasma. 1 The measurement can be obtained through several methods:

• Automated cell counters provide the most accurate and reproducible hematocrit values, using electrical impedance or optical methods to calculate the percentage based on red blood cell count and mean corpuscular volume. 2
• Microhematocrit centrifugation involves spinning a capillary tube of blood at high speed to physically separate red cells from plasma, then reading the percentage on a calibrated scale. 3, 4
• Conductivity-based methods estimate hematocrit by measuring blood conductivity in point-of-care analyzers, though these can be inaccurate in patients with abnormal plasma osmolality or protein concentrations. 5

Normal Reference Ranges

The physiological hematocrit varies by sex, age, and altitude:

• Adult males: 42–54% (hemoglobin 13.5–17.5 g/dL) 1
• Adult females: 38–46% (hemoglobin 12–16 g/dL) 1
• Menstruating women: typically 41 ± 5% 2
• Post-menopausal women and men: typically 47 ± 6% 2

Gender differences emerge at puberty due to testosterone (which stimulates erythropoiesis) and estrogen (which has opposite effects). 2

Altitude Adjustments

Hematocrit increases physiologically with altitude due to hypoxia-driven erythropoietin production. 2 The expected increase ranges from +0.2 g/dL hemoglobin at 1,000 meters to +4.5 g/dL at 4,500 meters elevation. 2

Clinical Significance

Elevated Hematocrit (Erythrocytosis)

True erythrocytosis is defined as hemoglobin >18.5 g/dL in men or >16.5 g/dL in women, corresponding to hematocrit >52% in men or >48% in women. 2, 1

Elevated hematocrit requires investigation when:

• Hematocrit exceeds 60% in men or 55% in women at sea level 1, 3
• Values lie above the 95th percentile after adjusting for sex, race, and altitude 1
• Borderline elevation occurs with thrombocytosis, leukocytosis, splenomegaly, or unusual thrombosis 1

The primary clinical concern with elevated hematocrit is increased thrombotic risk due to blood hyperviscosity. 2, 6 However, the relationship between hematocrit and oxygen delivery is complex—while higher hematocrit increases oxygen-carrying capacity, it also increases viscosity and flow resistance. 6

Causes of Elevated Hematocrit

Primary polycythemia (polycythemia vera): A JAK2-mutation-driven myeloproliferative neoplasm characterized by autonomous red cell production, often accompanied by thrombocytosis, leukocytosis, and splenomegaly. 2, 3

Secondary erythrocytosis: A compensatory physiological response to tissue hypoxia from conditions including:

• Chronic lung disease (COPD) 2
• Obstructive sleep apnea 2
• Cyanotic congenital heart disease with right-to-left shunting 2
• Smoking (carbon monoxide-induced tissue hypoxia) 2
• High altitude residence 2
• Erythropoietin-secreting tumors (renal cell carcinoma, hepatocellular carcinoma) 2
• Testosterone therapy 2

Relative polycythemia: Plasma volume depletion from dehydration, diuretics, or stress polycythemia (Gaisböck syndrome) without true increase in red cell mass. 2

Low Hematocrit (Anemia)

Anemia is defined as hematocrit <39% in men or <36% in women, corresponding to hemoglobin <13 g/dL and <12 g/dL respectively. 1

• In chronic kidney disease, hematocrit begins declining when eGFR falls below 60 mL/min/1.73 m². 1
• When eGFR is <20 mL/min/1.73 m², average hematocrit falls by approximately 5.3% in women and 10.0% in men. 1
• Anemia is not a normal consequence of aging—any low hematocrit warrants investigation for underlying pathology. 2

Hematocrit vs. Hemoglobin for Clinical Decision-Making

Hemoglobin is the preferred measurement over hematocrit for diagnosis and monitoring because it is more accurate, reproducible, and stable. 2, 1

Key advantages of hemoglobin:

• Hematocrit can falsely increase by 2–4% when blood samples are stored longer than 8 hours due to red cell swelling, while hemoglobin remains stable. 2
• Hyperglycemia falsely elevates mean corpuscular volume and calculated hematocrit but does not affect hemoglobin measurement. 2
• Hemoglobin shows less inter-laboratory variability in automated analyzer measurements. 2

Relationship Between Hematocrit and Hemoglobin

The traditional rule that "hematocrit equals three times hemoglobin" (Hct% = 3 × Hgb g/dL) is an approximation that does not hold accurately across all ages and clinical conditions. 7

• The actual Hct/Hgb ratio varies with age in a non-linear fashion, approaching but not consistently equaling 3. 7
• In pediatric populations, using the "×3 rule" leads to significant misclassification of anemia, with only fair-to-moderate agreement between hematocrit-based and hemoglobin-based anemia definitions. 7
• The ratio changes with both age and absolute hemoglobin level—hematocrit decreases with age at high hemoglobin levels but increases with age at low hemoglobin levels. 7

Optimal Hematocrit for Tissue Oxygenation

The concept of an "optimal" hematocrit balances oxygen-carrying capacity against blood viscosity and flow resistance. 6

• In vitro studies and healthy athletes suggest an optimal hematocrit of 50–70% for maximal oxygen transport. 6
• However, in clinical disease states, restrictive strategies targeting lower hematocrit levels (20–24%, corresponding to hemoglobin 7–8 g/dL) consistently show better outcomes in chronic kidney disease, heart failure, critical care, and surgery. 6
• This discrepancy reflects that diseased states involve reduced perfusion pressures, endothelial dysfunction, and altered microvascular flow that make higher hematocrit detrimental. 6

Management Thresholds

For Polycythemia Vera

Maintain hematocrit strictly below 45% through therapeutic phlebotomy to reduce thrombotic risk. 2, 1 The landmark CYTO-PV trial demonstrated that maintaining hematocrit <45% reduced cardiovascular death or major thrombosis from 9.8% to 2.7% (HR 3.91, P=0.007). 2

• A slightly lower target of approximately 42% is reasonable for women and African Americans due to physiological differences in baseline values. 2
• Add low-dose aspirin 81–100 mg daily as the second cornerstone of therapy. 2, 1

For Secondary Erythrocytosis

Routine phlebotomy is contraindicated in secondary erythrocytosis because it causes iron depletion, decreased oxygen-carrying capacity, and paradoxically increases stroke risk. 2, 1

Phlebotomy in secondary erythrocytosis is indicated only when ALL of the following criteria are met: 2, 1

• Hemoglobin >20 g/dL AND hematocrit >65%
• Documented symptoms of hyperviscosity (headache, blurred vision, confusion)
• Patient is adequately hydrated
• Iron deficiency has been excluded (transferrin saturation ≥20%)
• Hematocrit remains elevated above patient's baseline despite hydration

First-line therapy for suspected hyperviscosity is aggressive rehydration with oral fluids or intravenous normal saline—not phlebotomy. 2, 1

Common Pitfalls

• Never perform phlebotomy without equal-volume fluid replacement, as this increases hemoconcentration and stroke risk. 2
• Do not overlook coexisting iron deficiency, which mimics hyperviscosity symptoms but requires iron supplementation rather than phlebotomy. 2, 1
• Mean corpuscular volume is unreliable for screening iron deficiency in erythrocytosis—use serum ferritin, transferrin saturation, and iron levels instead. 2
• In cyanotic congenital heart disease, the elevated hematocrit is a compensatory mechanism to optimize oxygen transport and should not be routinely reduced. 2, 1