Elevated Red Blood Cell Count in Obstructive Sleep Apnea
An elevated RBC count in OSA patients is paradoxically uncommon despite chronic intermittent hypoxia, occurring in only 2% of mild-to-moderate OSA and 6% of severe OSA cases, due to offsetting mechanisms including neocytolysis (hemolysis of newly formed RBCs) and inflammation-induced hepcidin suppression of erythropoiesis. 1, 2
Understanding the Pathophysiology
Why Erythrocytosis is Expected but Rarely Occurs
Intermittent hypoxia during sleep in OSA should theoretically trigger compensatory erythrocytosis through increased erythropoietin production, similar to other chronic hypoxic conditions 1
However, >98% of OSA patients do not develop elevated hemoglobin despite experiencing repetitive nocturnal hypoxemia 1
The absence of erythrocytosis results from two counterbalancing mechanisms:
- Neocytolysis: Newly generated RBCs produced during hypoxic episodes undergo hemolysis when oxygen levels normalize, driven by increased reactive oxygen species from expanded reticulocyte mitochondria and downregulation of the antioxidant catalase by hypoxia-stimulated microRNA-21 1
- Inflammation-mediated suppression: Elevated hepcidin levels from chronic inflammation limit iron availability for erythropoiesis, preventing adequate RBC production 1
Red cell mass remains normal when measured by radionuclide labeling, excluding the possibility that plasma volume expansion masks underlying erythrocytosis 1
Clinical Markers of Severity
Red cell distribution width (RDW) is elevated in OSA patients compared to healthy controls (13.40 vs 13.15, P=0.036) and correlates positively with apnea-hypopnea index (AHI) severity 3, 4, 5
RDW serves as an economical marker to initially assess OSA severity and cardiovascular risk, with a cut-off of 14.45 providing 81% sensitivity and 75% specificity for predicting cardiovascular disease in OSA 5
RDW correlates with inflammatory markers (C-reactive protein) and is an independent predictor of cardiovascular disease in OSA patients (OR=3.095,95% CI: 1.69-5.66) 5
Management Approach
When Polycythemia is Present (Rare Cases)
Confirm true polycythemia by measuring red cell mass directly rather than relying solely on hemoglobin/hematocrit, as plasma volume changes can confound interpretation 1
Initiate CPAP therapy as first-line treatment for diagnosed OSA, which is the standard recommendation from the American College of Physicians 6
CPAP reduces hemoglobin by 3.76 g/L (95% CI -4.73 to -2.80 g/L) and hematocrit by 1.1% (95% CI -1.4 to -0.9%) in pooled analyses, though these reductions are modest 2
Monitor response after one year of CPAP therapy, though RDW levels may not significantly change despite effective OSA treatment 3
Addressing Underlying OSA
Confirm OSA diagnosis with polysomnography (PSG), which is the standard method requiring measurement of EEG, EOG, chin EMG, airflow, oxygen saturation, respiratory effort, and ECG 7
Portable monitors may be used in patients with high pretest likelihood of moderate-to-severe OSA as part of comprehensive sleep evaluation, but are not indicated in those with major comorbidities 7
Weight loss is the most effective non-pharmacological intervention, as obesity is present in >70% of adult OSA patients and directly correlates with disease severity 6
Cardiovascular Risk Management
Screen for and aggressively manage hypertension, which is present in ≥80% of patients with resistant hypertension who have OSA 8, 6
Initiate two-drug antihypertensive combination with a RAS blocker plus either a dihydropyridine calcium channel blocker or thiazide/thiazide-like diuretic, preferably as a single-pill combination 6
Target systolic blood pressure to 120-129 mmHg in most adults if treatment is well tolerated 6
Recognize that CPAP produces only modest BP reductions (2-3 mmHg average), though it significantly reduces cardiovascular events (adjusted HR 0.34,95% CI 0.20-0.58) 8, 9
Common Pitfalls to Avoid
Do not assume polycythemia is present based solely on OSA diagnosis—the prevalence is only 2-6% depending on severity 2
Do not rely on symptom-based questionnaires alone for screening OSA, as overnight ambulatory polysomnography is required for definitive diagnosis 7
Do not expect RDW to normalize with CPAP treatment, as this marker remains elevated despite effective OSA therapy 3
Do not discontinue antihypertensive medications when initiating CPAP, as blood pressure reductions from CPAP alone are insufficient for most patients 8, 9
Do not overlook inflammation and iron metabolism as contributors to the hematologic profile in OSA—hepcidin elevation limits erythropoiesis independent of hypoxia 1