Diagnosis, management, and outcomes of hypoxia-associated erythrocytosis: A systematic review.

Hypoxia is the most common cause of secondary erythrocytosis, with implicated respiratory conditions including chronic obstructive pulmonary disease (COPD), obstructive sleep apnea (OSA), and exposures such as smoking. We conducted a systematic review to inform the clinical management of hypoxia-associated erythrocytosis. Following PRISMA guidelines, we performed a systematic literature search in MEDLINE, EMBASE, CENTRAL (all via Ovid), and Google Scholar. Of 2,233 articles screened, 42 studies were included, which reported on patients with COPD (20 studies), OSA (11 studies), smoking (9 studies), unspecified respiratory disease (4 studies), COVID-19 (2 studies), pulmonary arteriovenous malformations (1 study), and idiopathic pulmonary fibrosis (1 study). Erythrocytosis was present in up to 53.6% of patients with COPD in included studies, and was generally associated with increased disease severity. Thromboembolic events were reported in up to 39% of COPD patients with erythrocytosis (versus up to 14% in COPD patients without erythrocytosis), mostly in the setting of hospitalization. Up to 15% of patients with OSA had erythrocytosis in included studies, with lower thromboembolic risk compared to patients with other chronic respiratory disease. Treatment with continuous positive airway pressure improved hematologic parameters. In smokers with erythrocytosis, up to 19.6% had thromboembolic events. Hypoxia-associated erythrocytosis is a heterogenous condition, for which there is a lack of consensus regarding clinical approach. Risks of thromboembolism and mortality may relate to disease-specific factors and comorbidities, rather than erythrocytosis itself. We offer recommendations for clinical practice within the scope of this systematic review, including referral to a respirologist for therapies to improve oxygenation.