What causes a slightly elevated hematocrit (Hct)?

Causes of Slightly Elevated Hematocrit

A slightly elevated hematocrit most commonly results from relative polycythemia (plasma volume depletion from dehydration or diuretic use), smoking-induced erythrocytosis, or physiological variations related to sex, altitude, or chronic hypoxemia from conditions like sleep apnea or lung disease. 1

Primary Categories of Elevated Hematocrit

Relative Polycythemia (Pseudopolycythemia)

• Dehydration is the most common cause of mildly elevated hematocrit, where plasma volume decreases while red cell mass remains normal 1
• Diuretic use can cause plasma volume contraction leading to hemoconcentration 1
• Stress polycythemia (Gaisböck syndrome) presents with elevated hematocrit but normal red cell mass 1
• These conditions resolve with adequate hydration and do not represent true erythrocytosis 2

Secondary Erythrocytosis (Hypoxia-Driven)

• Smoking is the single most frequent cause of elevated hematocrit in clinical practice, producing "smoker's polycythemia" through chronic carbon monoxide exposure that stimulates erythropoietin production 1, 3
• Obstructive sleep apnea causes nocturnal hypoxemia that drives compensatory erythropoietin production 1, 2
• Chronic lung disease (COPD, interstitial lung disease) leads to chronic hypoxemia and secondary erythrocytosis 1, 4
• Cyanotic congenital heart disease with right-to-left shunting results in arterial hypoxemia and compensatory erythrocytosis 1, 2
• High altitude residence causes physiologically appropriate increases in hemoglobin and hematocrit (e.g., +0.8 g/dL at 2,000 meters) 1

Secondary Erythrocytosis (Hypoxia-Independent)

• Testosterone therapy (prescribed or unprescribed) is an increasingly common cause in younger adults 1
• Erythropoietin-producing tumors including renal cell carcinoma, hepatocellular carcinoma, pheochromocytoma, uterine leiomyoma, and meningioma 1
• Exogenous erythropoietin therapy in patients with chronic kidney disease 1

Primary Polycythemia

• Polycythemia vera is a myeloproliferative neoplasm with JAK2 mutation present in up to 97% of cases 1, 2
• Typically presents with hematocrit >55% in men or >49.5% in women, often accompanied by splenomegaly, aquagenic pruritus, or thrombocytosis 1, 3

Physiological Variations

• Sex differences: Adult males and post-menopausal females normally have hematocrit of 47 ± 6%, while menstruating females have 41 ± 5% 5, 1
• Age-related changes: Hemoglobin and hematocrit values vary significantly throughout childhood and stabilize in adulthood 5

Diagnostic Approach to Slightly Elevated Hematocrit

Initial Confirmation

• Repeat the measurement before pursuing extensive workup, as a single elevated value is unreliable 1, 2
• Confirm true elevation: hemoglobin >18.5 g/dL in men or >16.5 g/dL in women, hematocrit >55% in men or >49.5% in women 1

Essential Laboratory Evaluation

• Complete blood count with red cell indices to assess white blood cell and platelet counts (elevated in polycythemia vera) 1
• Serum ferritin and transferrin saturation to identify coexisting iron deficiency, which can mask erythrocytosis 1
• Reticulocyte count to evaluate bone marrow response 1

Distinguishing Primary from Secondary Causes

• JAK2 mutation testing (exon 14 and exon 12) should be performed if polycythemia vera is suspected 1, 2
• Erythropoietin level: Low or normal in polycythemia vera, elevated in secondary erythrocytosis 1
• Evaluate for hypoxic causes: Obtain oxygen saturation, consider sleep study if nocturnal hypoxemia suspected, assess smoking history 1

Critical Clinical Pearls

Common Pitfalls to Avoid

• Do not assume the 3:1 ratio between hematocrit and hemoglobin is accurate—this relationship varies with age and clinical conditions 5, 6
• Hemoglobin is more reliable than hematocrit for monitoring because hematocrit can falsely increase by 2-4% with prolonged sample storage, while hemoglobin remains stable 5, 1
• Hyperglycemia falsely elevates hematocrit but does not affect hemoglobin measurement 5, 1
• Iron deficiency can coexist with erythrocytosis, particularly in smokers and patients with polycythemia vera, causing microcytic polycythemia 1, 2

When to Refer

• Immediate hematology referral is warranted for JAK2-positive patients, hemoglobin >20 g/dL with hyperviscosity symptoms, or unexplained splenomegaly 1
• Hematocrit >60% in men or >55% in women always indicates absolute polycythemia requiring further evaluation 3

Management Considerations

• Address the underlying cause first: smoking cessation for smoker's polycythemia, CPAP for sleep apnea, management of chronic lung disease 1, 2
• Therapeutic phlebotomy is rarely indicated for slightly elevated hematocrit and should only be performed when hemoglobin >20 g/dL and hematocrit >65% with hyperviscosity symptoms 1, 2
• Hydration is first-line therapy for suspected hyperviscosity symptoms, not phlebotomy 2