What is the likely cause of polycythemia in a patient with elevated hemoglobin levels?

Obstructive Sleep Apnea as the Most Likely Cause

In this obese patient with chronic fatigue and mild polycythemia (hemoglobin 17.4 g/dL), obstructive sleep apnea is the most likely cause, driven by his BMI of 36 kg/m² creating chronic intermittent hypoxia that triggers compensatory erythrocytosis. 1

Why OSA is the Leading Diagnosis

Clinical Profile Strongly Suggests OSA

• Obesity (BMI 36 kg/m²) is the strongest risk factor for obstructive sleep apnea, which causes chronic intermittent hypoxemia leading to secondary polycythemia 1
• The patient's report of "adequate sleep" is a classic pitfall – patients with OSA are typically unaware of their sleep fragmentation and nocturnal arousals, presenting instead with unexplained chronic fatigue 1
• The hemoglobin level of 17.4 g/dL represents mild polycythemia that is more consistent with secondary causes than polycythemia vera, which typically presents with more marked elevations (often >18.5 g/dL in men) 1

Pathophysiology of OSA-Induced Polycythemia

• Chronic intermittent hypoxia during sleep triggers compensatory erythropoiesis through elevated erythropoietin (EPO) production 2, 1
• The hypoxia-driven mechanism distinguishes this from primary polycythemia vera, where EPO levels are low or inappropriately normal 2, 3

Diagnostic Approach to Confirm OSA

Step 1: Order Polysomnography (Sleep Study)

• Polysomnography is the definitive test to confirm obstructive sleep apnea as the cause of chronic hypoxemia 1
• Nocturnal oximetry during the sleep study will document the intermittent hypoxemia that drives erythrocytosis 1

Step 2: Measure Serum Erythropoietin Level

• Serum EPO level is the critical discriminator between primary and secondary polycythemia 2, 3
• Expected finding: elevated or high-normal EPO in hypoxia-driven secondary polycythemia (though levels may normalize after hemoglobin stabilizes at a higher baseline) 1
• Low or inappropriately normal EPO would suggest polycythemia vera and require JAK2 mutation testing 2, 3

Step 3: Exclude Other Secondary Causes (If OSA Not Confirmed)

• Arterial blood gas or pulse oximetry can document daytime hypoxemia if chronic lung disease is suspected 2
• Chest X-ray to evaluate for chronic obstructive pulmonary disease or pulmonary fibrosis 2
• Abdominal imaging (ultrasound or CT) only if EPO is elevated without hypoxia, to screen for EPO-producing tumors (renal cell carcinoma, hepatocellular carcinoma) 2

Why Not Polycythemia Vera?

Clinical Features Argue Against PV

• The mild elevation in hemoglobin (17.4 g/dL) is less typical of polycythemia vera, which usually presents with hemoglobin >18.5 g/dL in men 4, 1
• No mention of thrombocytosis (present in 53% of PV cases) or leukocytosis (present in 49% of PV cases), which are characteristic of the panmyeloid hyperplasia seen in PV 3
• The clinical context of obesity and fatigue strongly points toward a secondary hypoxic cause rather than a primary clonal disorder 1

PV Would Require Different Findings

• JAK2 V617F mutation (present in >95% of PV cases) would need to be positive 4, 5
• Serum EPO would be low or inappropriately normal, not elevated 2, 3, 5
• Bone marrow biopsy would show panmyelosis with prominent erythroid and megakaryocytic proliferation 4

Critical Pitfalls to Avoid

Don't Accept "Adequate Sleep" at Face Value

• Patients with OSA are unaware of their sleep fragmentation – they perceive they sleep enough but experience chronic fatigue due to poor sleep quality 1
• The absence of reported snoring or witnessed apneas does not exclude OSA, especially in obese patients 1

Don't Rush to Diagnose Polycythemia Vera

• Always exclude secondary causes first, especially in an obese patient with fatigue 1
• The combination of obesity, fatigue, and mild polycythemia should trigger immediate consideration of OSA before pursuing expensive or invasive testing for PV 1

Don't Overlook Smoking History

• While this patient does not smoke, smoker's polycythemia is a real condition caused by chronic carbon monoxide exposure (which binds hemoglobin with 200-250 times greater affinity than oxygen), creating functional hypoxia that resolves with smoking cessation 2

Expected Management Once OSA Confirmed

Primary Treatment

• CPAP therapy is the primary treatment for obstructive sleep apnea, which should resolve the polycythemia by eliminating nocturnal hypoxemia 1
• Weight loss is essential as it directly addresses the underlying pathophysiology of OSA 1

Expected Outcome

• Resolution of polycythemia typically occurs within months of effective CPAP therapy and weight loss 1
• Persistent polycythemia despite adequate OSA treatment would warrant re-evaluation for other causes 2