Background: Polycythemia vera (PV), the most common myeloproliferative neoplasm, is characterized by erythrocytosis and often complicated by venous and arterial thrombosis. Obstructive sleep apnea (OSA), a cause of secondary erythrocytosis, is an independent risk factor in the development of deep vein thrombosis (DVT) and stroke. It could be hypothesized that the coexistence of PV and OSA could have an additive or synergistic increase in risk of venous or arterial thrombosis, yet little evidence exists to study this relationship.

Methods: We conducted a retrospective cohort study using the National Inpatient Sample (NIS) database from 2017 to 2021, part of the Healthcare Cost and Utilization Project (HCUP). Adult patients hospitalized with a diagnosis of polycythemia vera (PV) were identified and stratified based on the presence or absence of co-diagnosed obstructive sleep apnea (OSA). National estimates were generated using the discharge weight variable “DISCWT.” Categorical variables were compared using Pearson's Chi-square test, and continuous variables were assessed using Student's t-tests or one-way ANOVA. The primary outcome was in-hospital mortality. Secondary outcomes included length of stay, total hospitalization charges, incidence of acute deep venous thrombosis (DVT), acute pulmonary embolism (PE), acute ischemic stroke, and use of mechanical ventilation. Multivariate logistic and linear regression models were used to adjust for confounders including age, gender, and Charlson Comorbidity Index.

Results: A total of 21,311 hospitalized patients with PV were included, of whom 2,897 had a concurrent diagnosis of OSA. After adjusting for confounders, patients with PV and OSA had significantly lower odds of in-hospital mortality compared to those without OSA (2.66% vs 4.21%, aOR: 0.67; 95% CI: 0.52–0.85; p = 0.001). They also had lower odds of developing acute DVT (2.14% vs 2.83%, aOR: 0.76; 95% CI: 0.58–0.99; p = 0.041), acute ischemic stroke (3.62% vs 4.27%, aOR: 0.78; 95% CI: 0.63–0.97; p = 0.023), and requiring mechanical ventilation (3.83% vs 4.35%, aOR: 0.77; 95% CI: 0.63–0.95; p = 0.013). There was no significant difference in the incidence of acute PE (2.9% vs 3.4%, aOR: 0.95; 95% CI: 0.75–1.2; p = 0.651). Patients with OSA also had a shorter length of stay (5.76 vs 6.39 days, aOR: 0.90; 95% CI: 0.86–0.94; p < 0.001). There was no significant difference in total hospitalization charges between the two groups ($17,393 vs $17,282, aOR: 1.01; 95% CI: 0.94–1.07; p = 0.846).Conclusion: As an independent risk factor for VTE and stroke, it is paradoxical that concomitant existence of OSA in patients with PV would be associated with a lower incidence of these complications. This dissonance may be related to the underdiagnosis of OSA, which occurs in 82% and 93% of men and women respectively. As the intermittent hypoxia that occurs in untreated OSA results in increased sympathetic activity, endothelial dysfunction, hypercoagulability and secondary erythrocytosis, it could be theoretized that together these disparate drivers of erythrocytosis could additively increase the risk of VTE development. Diagnosis and subsequent treatment of the innate hypercoagulability of OSA in and of itself could explain the demonstrated reduction in odds of developing acute DVT and acute ischemic stroke. While current PV treatment recommendations suggest a thorough assessment of cardiovascular risk, including screening for OSA, these findings suggest there may be benefit to investigating the role of aggressive OSA screening to reduce risk of VTE and stroke.

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2025
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