What are the possible causes of an elevated hemoglobin (16.6 g/dL) and hematocrit (50.2 %) in an 85‑year‑old woman?

Elevated Hemoglobin and Hematocrit in an 85-Year-Old Woman

In an 85-year-old woman with hemoglobin 16.6 g/dL and hematocrit 50.2%, the most likely causes are secondary erythrocytosis from chronic hypoxemia (chronic lung disease, sleep apnea, smoking), relative polycythemia from dehydration or diuretic use, or less commonly, polycythemia vera—though her values fall below the WHO diagnostic threshold of hemoglobin >16.5 g/dL for women, making PV diagnosis require additional criteria. 1, 2

Understanding the Laboratory Values

These values represent mild elevation above normal ranges for elderly women. According to population data, the 95th percentile for hemoglobin in women aged 70 years and over is approximately 15.2–15.6 g/dL, placing this patient's value of 16.6 g/dL above the normal range but not dramatically elevated. 1 The hematocrit of 50.2% similarly exceeds the typical range for elderly women (95th percentile approximately 47–48%). 1

Importantly, these values do NOT meet the WHO major criterion threshold for polycythemia vera diagnosis in women (hemoglobin >16.5 g/dL or hematocrit >48%), though they are very close. 1, 2 This distinction is critical because it determines the diagnostic pathway.

Primary Differential Diagnosis

Secondary Erythrocytosis (Most Common in This Age Group)

Chronic hypoxemia is the leading cause of secondary erythrocytosis in elderly patients. 3, 4 Specific etiologies include:

• Chronic obstructive pulmonary disease (COPD) or other chronic lung disease causing persistent hypoxemia drives compensatory erythropoietin production. 3
• Obstructive sleep apnea produces nocturnal hypoxemia that stimulates erythropoietin secretion, particularly common in elderly patients. 3
• Smoking causes "smoker's polycythemia" through chronic carbon monoxide exposure, which creates tissue hypoxia and triggers erythropoietin production; this resolves with smoking cessation. 3
• Congestive heart failure with chronic hypoxemia can drive compensatory erythrocytosis. 3

Relative Polycythemia (Plasma Volume Contraction)

Dehydration and diuretic use are extremely common in elderly patients and can elevate hemoglobin/hematocrit through plasma volume depletion rather than true red cell mass expansion. 3 This is particularly important to exclude before pursuing extensive workup, as it represents a benign, reversible cause.

Polycythemia Vera (Less Likely but Must Be Excluded)

While this patient's hemoglobin is technically below the WHO threshold of >16.5 g/dL for women, polycythemia vera can still be diagnosed if JAK2 mutation is present along with sufficient minor criteria (low erythropoietin, bone marrow hypercellularity, or endogenous erythroid colony formation). 2, 5 JAK2 mutations are found in >95% of PV cases. 1, 2

Masked polycythemia vera—where PV exists despite normal or near-normal hemoglobin due to concurrent iron deficiency or blood loss—is a recognized variant that can present with thrombosis as the first manifestation. 5

Recommended Diagnostic Algorithm

Step 1: Confirm True Erythrocytosis and Assess Hydration

• Repeat complete blood count after ensuring adequate hydration, as a single measurement is unreliable for diagnosis. 3
• Assess volume status clinically and review diuretic medications, as relative polycythemia from plasma contraction is common and benign. 3

Step 2: Initial Laboratory Panel

• Complete blood count with red cell indices, reticulocyte count, and peripheral blood smear to assess for trilineage abnormalities suggesting myeloproliferative disease. 3
• Serum ferritin and transferrin saturation to identify iron deficiency, which can mask true erythrocytosis by lowering hemoglobin while red cell mass remains elevated. 2, 3
• C-reactive protein to assess for inflammatory conditions. 3

Step 3: Evaluate for Secondary Causes

• Pulse oximetry or arterial blood gas to document hypoxemia; arterial oxygen saturation <92% indicates secondary polycythemia from hypoxia. 3
• Detailed smoking history and quantification of pack-years. 3
• Sleep study if clinical features suggest obstructive sleep apnea (snoring, witnessed apneas, daytime somnolence). 3
• Pulmonary function tests and chest imaging if COPD or other lung disease is suspected. 3
• Medication review for testosterone or erythropoietin use. 3

Step 4: JAK2 Mutation Testing (If Secondary Causes Excluded)

JAK2 V617F mutation testing is the first-line molecular assay and should be ordered if secondary causes are not identified. 2 This test detects >90–95% of PV cases. 2

If JAK2 V617F is negative, JAK2 exon 12 mutation analysis should be performed, accounting for an additional 2–3% of PV cases. 2

Step 5: Serum Erythropoietin Level

Low serum erythropoietin (below laboratory reference range) serves as a WHO minor criterion supporting PV diagnosis, but it cannot diagnose PV alone. 2 Low EPO helps differentiate primary from secondary erythrocytosis. 2

Step 6: Bone Marrow Biopsy (If Indicated)

Bone marrow biopsy is required if JAK2 mutation is positive to confirm PV diagnosis and assess for hypercellularity with trilineage growth and pleomorphic megakaryocytes. 2, 3

Bone marrow biopsy should also be considered if diagnosis remains unclear after initial workup to exclude other myeloid neoplasms. 3

Management Considerations

If Secondary Erythrocytosis Is Confirmed

Treatment focuses on the underlying condition: smoking cessation for smoker's polycythemia, CPAP therapy for obstructive sleep apnea, management of COPD, or supplemental oxygen for documented hypoxemia. 3

Therapeutic phlebotomy is NOT indicated for mild secondary erythrocytosis at these hemoglobin/hematocrit levels. 3 Phlebotomy should only be considered when hemoglobin >20 g/dL AND hematocrit >65% with documented hyperviscosity symptoms after excluding dehydration. 3

Routine phlebotomy is explicitly contraindicated in secondary erythrocytosis because it causes iron depletion, decreased oxygen-carrying capacity, and paradoxically increases stroke risk. 3

If Polycythemia Vera Is Diagnosed

Maintain hematocrit strictly below 45% through therapeutic phlebotomy to reduce thrombotic risk, as demonstrated by the CYTO-PV trial. 3

Initiate low-dose aspirin (81–100 mg daily) as the second cornerstone of therapy for thrombosis prevention. 3

Refer immediately to hematology for ongoing management and consideration of cytoreductive therapy if indicated. 3

Critical Pitfalls to Avoid

• Do not diagnose PV solely on the basis of low erythropoietin, even when hemoglobin is mildly elevated; JAK2 mutation testing is mandatory. 2
• Do not perform routine phlebotomy in secondary erythrocytosis, as this leads to iron depletion and increased stroke risk. 3
• Do not overlook coexisting iron deficiency, which can mask true erythrocytosis and requires iron supplementation rather than phlebotomy. 3
• Do not assume anemia or lower hemoglobin is "normal aging" in elderly patients; anemia reflects poor health and warrants investigation. 1, 6, 7
• Do not forget that hemoglobin declines with age in men but remains stable in women, so this patient's elevated value is particularly significant. 1, 7