What is the frequency of erythrocytosis (increased red blood cell count) in patients with sleep apnea (obstructive sleep apnea syndrome)?

Erythrocytosis in Sleep Apnea: Prevalence and Clinical Significance

Erythrocytosis is relatively uncommon in patients with obstructive sleep apnea, with studies showing that less than 2% of OSA patients develop clinically significant erythrocytosis despite intermittent hypoxia during sleep. 1

Epidemiology and Prevalence

The relationship between OSA and erythrocytosis has been investigated in multiple studies with the following findings:

• In a large study of 1,604 veterans with suspected OSA, only 1.6% had clinical erythrocytosis 1
• A meta-analysis of 11 studies with 4,608 OSA patients found that while hematocrit values were statistically higher in OSA patients compared to controls, the elevation was modest and typically remained within normal range 2
• A recent analysis of 527 OSA patients found that more than 98% did not have elevated hemoglobin levels despite experiencing intermittent hypoxia 3

Severity Relationship

The association between erythrocytosis and OSA appears to be related to disease severity:

• Significant differences in hematocrit values between patients and controls were only observed in severe OSA groups 2
• The frequency of cardiac arrhythmias, including nocturnal ones, increases with the increased severity of sleep apnea-hypopnea syndrome 4
• Hematocrit levels correlate more strongly with hypoxemia parameters than with the apnea-hypopnea index (AHI) 1

Pathophysiological Mechanisms

Several mechanisms explain why most OSA patients don't develop the expected erythrocytosis despite intermittent hypoxia:

1. Compensatory mechanisms: While OSA patients show accelerated erythropoiesis (increased erythropoietin and reticulocytosis), this is offset by neocytolysis (lysis of newly generated erythrocytes upon return to normoxia) 3

2. Oxidative stress: Increased reactive oxygen species from expanded reticulocytes' mitochondria and downregulation of antioxidant catalase contribute to this process 3

3. Inflammation: Inflammation-induced hepcidin limits iron availability for erythropoiesis 3

4. Oxygen saturation: Awake oxygen saturation and mean nocturnal oxygen saturation are more predictive of hematocrit levels than AHI 1

Clinical Implications

When evaluating patients with OSA for erythrocytosis:

• Focus on oxygen saturation parameters rather than AHI alone, as awake oxygen saturation (-0.17 points per Z-score, p<0.001) and mean nocturnal oxygen saturation (-0.08 points per Z-score, p=0.04) are inversely proportional to hematocrit 1

• Consider other factors that may contribute to elevated hematocrit in OSA patients:

  • Active tobacco use
  • Increased alcohol consumption
  • Exogenous testosterone therapy 1
  • Obesity (BMI is more predictive of red blood cell aggregation than AHI) 5

• Nocturnal oximetry may provide diagnostic utility in evaluating unexplained secondary polycythemia 1

Hemorheological Changes

Beyond erythrocytosis, other blood rheological changes in OSA patients include:

• Higher plasma viscosity in severe OSA patients compared to controls, both in morning (1.74±0.3 vs. 1.36±0.2 mPas) and evening (1.55±0.2 vs. 1.27±0.1 mPas) 6
• Morning plasma viscosity inversely correlates with mean nocturnal oxygen saturation 6
• Increased red blood cell aggregation, which appears to be primarily related to overweight/obesity rather than the sleep apnea itself 5

Monitoring Recommendations

For patients with OSA who are at risk for erythrocytosis:

• Monitor hematocrit or hemoglobin levels, particularly in patients with severe OSA and significant nocturnal hypoxemia
• Consider polysomnography in patients with unexplained nocturnal hypoxemia and erythrocytosis 1
• Be particularly vigilant in patients receiving testosterone replacement therapy, as injections appear to be associated with a greater risk of erythrocytosis than topical preparations 4

In conclusion, while erythrocytosis is physiologically expected in conditions with hypoxemia, it is relatively uncommon in OSA due to compensatory mechanisms. When it does occur, it is more closely associated with severe disease, significant nocturnal hypoxemia, and other contributing factors rather than the presence of OSA itself.