Is a hemoglobin of 16.8 g/dL in an otherwise healthy 16‑year‑old male concerning, and what evaluation or management is needed?

Hemoglobin 16.8 g/dL in a 16-Year-Old Male: Assessment and Management

A hemoglobin of 16.8 g/dL in an otherwise healthy 16-year-old male is within the normal range and requires no intervention. This value falls comfortably within the expected reference range for adolescent males and does not meet criteria for polycythemia vera or secondary erythrocytosis.

Normal Reference Range for Adolescent Males

• The WHO diagnostic criteria for polycythemia vera define elevated hemoglobin as >16.5 g/dL in men, making 16.8 g/dL only marginally above this threshold 1.
• However, this WHO threshold is designed to capture pathological erythrocytosis in adults, not to define the upper limit of normal in healthy adolescents 1.
• Normal hemoglobin values in healthy males typically range from 13.0-17.0 g/dL, with the upper reference limit often extending to 17.5 g/dL depending on the laboratory 2, 3.
• A hemoglobin of 16.8 g/dL represents a physiologically normal value for a 16-year-old male who is completing puberty, when testosterone-driven erythropoiesis naturally elevates hemoglobin levels 4.

When to Investigate Elevated Hemoglobin

Investigation is warranted only when hemoglobin exceeds 18.5 g/dL (or hematocrit >55.5%) in males, as this represents sustained absolute erythrocytosis requiring evaluation for polycythemia vera or secondary causes 1.

For values between 16.5-18.5 g/dL in young males, consider these modifying factors before pursuing workup:

• Smoking increases hemoglobin by 0.3-1.0 g/dL and is a common cause of relative erythrocytosis in young adults 2, 4.
• Altitude correction is necessary: hemoglobin increases by 0.2 g/dL at 1,000 meters, 0.5 g/dL at 1,500 meters, and 0.8 g/dL at 2,000 meters elevation 2.
• Obesity and dehydration cause relative (apparent) erythrocytosis by reducing plasma volume rather than increasing red cell mass 4.
• Obstructive sleep apnea from obesity is a frequent cause of secondary erythrocytosis in young adults 4.

Clinical Context from Young Adult Studies

A 20-year retrospective study of 426 young adults (ages 16-35) with elevated hemoglobin found 4:

• The majority (43%) were obese, 59% were smokers, and 38% used excess alcohol or recreational drugs 4.
• Among those investigated, 25 had absolute erythrocytosis (most commonly from hypoxia), 7 had relative erythrocytosis, and 24 remained unexplained 4.
• No cases of primary erythrocytosis (polycythemia vera) were identified in this young cohort 4.
• The study revealed that JAK2 mutation testing and EPO levels were performed in only 17.9% and 23.2% of cases respectively, highlighting that most young adults with mildly elevated hemoglobin do not require extensive workup 4.

Cardiovascular Risk Considerations

While hemoglobin levels ≥17.0 g/dL are associated with increased cardiovascular risk in older adults, a hemoglobin of 16.8 g/dL does not confer increased cardiac risk 5:

• A large cohort study found that hemoglobin ≥17.0 g/dL (not 16.8 g/dL) was associated with increased coronary artery disease risk (adjusted HR 1.22) 5.
• The optimal hemoglobin range for cardiovascular health is 15.0-17.0 g/dL in males, making 16.8 g/dL ideal 5.

Recommended Approach

No workup or intervention is needed for this patient. Reassure the patient and family that this value is normal for a healthy adolescent male 4, 3.

If the hemoglobin were >18.5 g/dL, then proceed with:

• Detailed history focusing on smoking, sleep symptoms (snoring, daytime somnolence), altitude residence, family history of polycythemia, and use of performance-enhancing substances 1, 4.
• Physical examination for splenomegaly, plethora, and signs of hypoxemia 1.
• Laboratory evaluation including hematocrit, JAK2 V617F mutation, serum erythropoietin level, and oxygen saturation 1, 4.
• Bone marrow biopsy only if JAK2 mutation is positive or clinical suspicion for polycythemia vera is high 1.