What are the causes of elevated hemoglobin?

What Causes High Hemoglobin?

Elevated hemoglobin results from either increased red blood cell production (polycythemia), hemoconcentration from volume depletion, or physiologic adaptation to chronic hypoxia—most commonly from high altitude, chronic lung disease, or testosterone therapy.

Primary Causes of Elevated Hemoglobin

Physiologic Adaptation to Hypoxia

• High altitude residence causes increased hemoglobin as a compensatory mechanism for decreased oxygen availability, with the magnitude varying by population—Andean residents show the highest increase at 1 g/dL per 1000 meters elevation, while other populations demonstrate smaller increases of 0.6 g/dL per 1000 meters 1
• Chronic obstructive pulmonary disease and other chronic respiratory conditions stimulate erythropoiesis through sustained hypoxemia 2
• Cardiac disease with right-to-left shunting reduces tissue oxygen delivery, triggering compensatory erythrocytosis 2

Testosterone and Erythropoiesis

• Testosterone therapy acts as a direct stimulus for erythropoiesis, increasing hemoglobin levels by 15-20% during treatment 2
• Hemoglobin levels rise from subnormal to mid-normal range within the first three months of testosterone replacement, with most changes occurring early in therapy 2
• Intramuscular testosterone injections carry substantially higher risk of erythrocytosis (43.8% of patients) compared to transdermal preparations (15.4% of patients), particularly when achieving supraphysiologic testosterone levels 2
• Hematocrit elevation above 52% occurs more frequently with injectable testosterone and represents a significant clinical concern, especially in elderly patients with underlying vascular disease 2

Erythropoietin Therapy

• Epoetin administration in chronic kidney disease patients increases hemoglobin levels as the primary therapeutic mechanism, with target hemoglobin values typically set between 10-12 g/dL 2
• Patients receiving erythropoietin-stimulating agents require monitoring for excessive hemoglobin rise, as levels above target ranges may increase cardiovascular risk 2

Secondary and Relative Causes

Hemoconcentration

• Volume depletion from dehydration, diuretic use, or fluid losses concentrates red blood cells, artificially elevating hemoglobin measurements without true increase in red cell mass 2

Genetic and Structural Hemoglobin Variants

• Hemoglobin variants including HbM disease and unstable hemoglobins can present with altered hemoglobin measurements, though these typically cause methemoglobinemia rather than true polycythemia 2, 3
• Alpha thalassemia variants such as HbH disease generally cause anemia rather than elevated hemoglobin, maintaining steady-state levels around 9-10 g/dL 4, 5

Critical Clinical Considerations

Risk Assessment

• Elderly patients with pre-existing cardiovascular disease face increased risk from elevated hemoglobin due to increased blood viscosity potentially aggravating coronary, cerebrovascular, or peripheral vascular disease 2
• Patients with chronic lung disease may have baseline hematocrit elevation that compounds with other causes of erythrocytosis, requiring lower treatment thresholds 2, 6

Monitoring Priorities

• Hematocrit values above 52% warrant intervention, particularly in testosterone-treated patients or those receiving erythropoietin therapy 2
• Cerebral oxygen delivery is optimized at normal sea-level hematocrit (40-45%), with both lower and higher values reducing tissue oxygen delivery despite changes in blood flow 2

Common Pitfalls

• Do not assume all elevated hemoglobin represents true polycythemia—rule out hemoconcentration from volume depletion before pursuing extensive workup 2
• In testosterone therapy, transdermal preparations should be preferentially considered over intramuscular injections to minimize erythrocytosis risk 2
• Recognize that supraphysiologic testosterone dosing (>300 mg weekly) substantially increases erythrocytosis risk beyond that seen with physiologic replacement 2