What causes an elevation in red blood cell (RBC) hemoglobin (H/H) over 3 months in an elderly male?

Causes of Elevated RBC Hemoglobin/Hematocrit Over 3 Months in an Elderly Male

The most common causes of rising hemoglobin and hematocrit over 3 months in an elderly male include secondary polycythemia from chronic hypoxia (smoking, COPD, obstructive sleep apnea), polycythemia vera (a JAK2-mutation-driven myeloproliferative neoplasm), relative polycythemia from dehydration or diuretic use, and less commonly, erythropoietin-secreting tumors or testosterone therapy. 1

Primary Diagnostic Considerations

Secondary Polycythemia (Hypoxia-Driven)

The most frequent cause in elderly males is chronic tissue hypoxia stimulating compensatory erythropoietin production:

• Smoking causes "smoker's polycythemia" through chronic carbon monoxide exposure, which creates tissue hypoxia and drives erythropoietin production; this resolves with smoking cessation 1
• Obstructive sleep apnea produces nocturnal hypoxemia that stimulates erythropoietin production and can cause progressive erythrocytosis over months 1
• Chronic obstructive pulmonary disease (COPD) and other chronic lung diseases cause persistent hypoxemia leading to compensatory red cell production 1

Polycythemia Vera (Primary Erythrocytosis)

• JAK2 mutation testing (both exon 14 and exon 12) should be performed when hemoglobin exceeds 18.5 g/dL in men or hematocrit exceeds 55% 1
• Diagnosis requires either both major WHO criteria (elevated hemoglobin/hematocrit/RBC mass AND JAK2 mutation) plus one minor criterion, OR the first major criterion plus two minor criteria 1

Relative Polycythemia

• Dehydration and diuretic use cause plasma volume contraction, concentrating red cells and falsely elevating hemoglobin/hematocrit without true increase in red cell mass 1
• This is particularly common in elderly patients on multiple medications for hypertension 2

Secondary Polycythemia (Hypoxia-Independent)

• Erythropoietin-secreting tumors including renal cell carcinoma, hepatocellular carcinoma, pheochromocytoma, uterine leiomyoma, and meningioma can produce erythropoietin independently 1
• Testosterone therapy (prescribed or unprescribed) stimulates erythropoietin production and red cell proliferation 1

Essential Diagnostic Workup

Initial Laboratory Evaluation

• Complete blood count with red cell indices to confirm true elevation and assess for iron deficiency (which can coexist with erythrocytosis) 1
• Reticulocyte count to evaluate bone marrow response 1
• Serum ferritin and transferrin saturation to identify concurrent iron deficiency, which is common in polycythemia vera and can cause microcytic polycythemia 1
• C-reactive protein (CRP) to assess for inflammatory conditions 1

Critical pitfall: High RDW with normal or low MCV suggests coexisting iron deficiency with erythrocytosis, which requires specific evaluation 1

Confirmatory Testing

• Erythropoietin level to differentiate primary (low EPO) from secondary (high EPO) causes 1
• JAK2 mutation testing if hemoglobin >18.5 g/dL or hematocrit >55% to evaluate for polycythemia vera 1
• Sleep study if nocturnal hypoxemia suspected based on history of snoring, witnessed apneas, or daytime somnolence 1
• Pulse oximetry or arterial blood gas to assess for chronic hypoxemia from pulmonary disease 1

Management Approach

When Phlebotomy Is Indicated

• Therapeutic phlebotomy is indicated ONLY when hemoglobin exceeds 20 g/dL and hematocrit exceeds 65% with symptoms of hyperviscosity (headache, dizziness, visual disturbances) after excluding dehydration 1
• Repeated routine phlebotomies are contraindicated due to risk of iron depletion, decreased oxygen-carrying capacity, and increased stroke risk 1
• When phlebotomy is performed, replace with equal volume of saline to prevent further hemoconcentration 1

Treatment of Underlying Causes

• For smoking-related polycythemia: Smoking cessation is the definitive treatment 1
• For obstructive sleep apnea: CPAP therapy addresses the underlying hypoxemia 1
• For COPD: Optimize pulmonary management and consider supplemental oxygen if hypoxemic 1
• For testosterone therapy: Dose adjustment or temporary discontinuation if hematocrit continues rising 1
• For polycythemia vera: Maintain hematocrit strictly below 45% through phlebotomy to reduce thrombotic risk, plus low-dose aspirin as second cornerstone of therapy 1

Special Considerations in Elderly Patients

• Avoid iron deficiency even in the presence of erythrocytosis, as iron-deficient red cells have reduced oxygen-carrying capacity and deformability, increasing stroke risk 1
• If iron deficiency is confirmed, cautious oral iron supplementation with close hemoglobin monitoring is necessary, as rapid increases in red cell mass can occur 1
• Hemoglobin is more accurate than hematocrit for monitoring because hematocrit can falsely increase by 2-4% with prolonged sample storage, while hemoglobin remains stable 1

Important Caveats

• Hydroxyurea can cause macrocytosis that resembles pernicious anemia but is self-limiting and unrelated to B12/folate deficiency; this may confuse the diagnostic picture if the patient is being treated for a myeloproliferative disorder 3
• Normal aging does NOT cause elevated hemoglobin—in fact, hemoglobin typically decreases slightly in men after age 60 and in women after age 70 4
• Evaluate for concurrent conditions that increase bleeding or thrombotic risk, as elderly patients often have multiple comorbidities requiring anticoagulation or antiplatelet therapy 5, 6