What causes an increase in hematocrit (Hct)?

Causes of Increased Hematocrit

Increased hematocrit results from either true polycythemia (increased red blood cell mass) or relative polycythemia (decreased plasma volume), with the most common causes being smoking, dehydration, chronic hypoxia, and polycythemia vera. 1

Primary Polycythemia (Clonal Disorders)

Polycythemia vera (PV) is a myeloproliferative neoplasm caused by clonal hematopoiesis where a single abnormal hematopoietic stem cell gains growth advantage, resulting in overproduction of red cells, granulocytes, and platelets. 2

• JAK2 mutations are present in up to 97% of PV cases and represent the key diagnostic marker. 1
• PV typically presents with splenomegaly, aquagenic pruritus, and erythromelalgia—symptoms that distinguish it from secondary causes. 3, 2
• The diagnosis requires either both major criteria (elevated hemoglobin/hematocrit AND JAK2 mutation) plus one minor criterion, OR the first major criterion plus two minor criteria. 1
• This is critical to identify because untreated PV carries significant thrombotic risk, with hematocrit >45% associated with increased cardiovascular death and major thrombotic events. 4, 5

Secondary Polycythemia (Physiological Response)

Hypoxia-Driven Causes

Chronic tissue hypoxia stimulates erythropoietin production, leading to compensatory erythrocytosis. 1

• Smoking is the most frequent cause of increased hematocrit, producing "smoker's polycythemia" through chronic carbon monoxide exposure that causes tissue hypoxia and stimulates erythropoietin production. 1, 3
• Chronic obstructive pulmonary disease (COPD) and other chronic lung diseases cause persistent hypoxemia. 1
• Obstructive sleep apnea produces nocturnal hypoxemia that drives erythropoietin production. 1, 5
• Cyanotic congenital heart disease with right-to-left shunting results in arterial hypoxemia, triggering compensatory erythrocytosis to optimize oxygen transport. 1, 5
• High altitude residence causes physiological increases in hemoglobin levels, with specific adjustments needed based on elevation (e.g., +1.9 g/dL at 3,000 meters). 1

Hypoxia-Independent Causes

Inappropriate erythropoietin production occurs independent of tissue oxygen status. 1

• Erythropoietin-producing tumors including renal cell carcinoma, hepatocellular carcinoma, pheochromocytoma, uterine leiomyoma, and meningioma can cause elevated hemoglobin levels. 1
• Exogenous erythropoietin therapy directly increases red blood cell production. 1
• Testosterone use (prescribed or unprescribed) causes erythrocytosis and should be considered in young adults with elevated hematocrit. 1

Relative Polycythemia (Decreased Plasma Volume)

Plasma volume depletion causes hematocrit elevation without true increase in red blood cell mass. 3, 2

• Dehydration from any cause reduces plasma volume, concentrating red blood cells. 1
• Diuretic use chronically reduces plasma volume. 1
• Burns cause significant plasma loss. 1
• Stress polycythemia (Gaisböck syndrome) represents chronic plasma volume contraction. 1

Physiological Variations

Gender and hormonal differences affect baseline hematocrit values. 1

• Males and post-menopausal females typically have hemoglobin 15.5 ± 2.0 g/dL and hematocrit 47 ± 6%, while menstruating females have hemoglobin 14.0 ± 2.0 g/dL and hematocrit 41 ± 5%. 1
• These differences emerge at puberty due to testosterone and estrogen effects. 1

Critical Diagnostic Thresholds

Absolute polycythemia is always present when hematocrit exceeds 60% in males or 55% in females. 3

• Hemoglobin >18.5 g/dL in men or >16.5 g/dL in women, or hematocrit >55% in men or >49.5% in women, defines erythrocytosis requiring evaluation. 1
• The association of increased hematocrit with splenomegaly, elevated white blood cell count, or thrombocytosis strongly indicates PV rather than secondary causes. 3

Common Pitfalls to Avoid

Do not assume all elevated hematocrit represents true polycythemia—always confirm with repeated measurements and assess hydration status, as relative polycythemia from dehydration is common and requires only fluid replacement. 1, 3

Do not overlook smoking history, as it is the most frequent cause and should prompt smoking cessation before extensive workup. 3

Do not miss iron deficiency coexisting with erythrocytosis, particularly in PV or cyanotic heart disease, which causes microcytic polycythemia with elevated RBC count but reduced hemoglobin. 1, 5