Air Pollution and Secondary Polycythemia: Pathophysiological Mechanisms, Clinical Implications, and Public Health Perspectives

Abstract

Background: Secondary polycythemia involves elevated red blood cell mass due to increased erythropoietin (EPO) production in response to tissue hypoxia or other stimuli, distinct from primary forms driven by intrinsic myeloproliferative defects. Air pollution, a major global health hazard affecting 4.2 million deaths annually, impairs oxygen delivery via carbon monoxide (CO) and fine particulate matter (PM2.5), potentially triggering pathological erythrocytosis through hypoxia-mediated EPO upregulation.
Objective: To synthesize evidence linking air pollution exposure to secondary polycythemia, encompassing mechanistic pathways, epidemiological data, clinical risks, and prevention strategies.
Methods: Systematic narrative review of PubMed, Scopus, and Web of Science databases (2005–2025) using keywords: "air pollution," "PM2.5," "CO," "secondary polycythemia," "erythrocytosis," "hypoxia," "EPO," "thrombosis," and related terms. Thematic synthesis organized findings into pathophysiology, epidemiology, clinical outcomes, and preventive strategies.
Results: PM2.5 exposure associates with erythrocytosis and thrombocytosis . CO-induced carboxyhemoglobin formation (200-fold affinity to hemoglobin) reduces functional oxygen delivery, mimicking chronic hypoxia and triggering HIF-2α-mediated EPO upregulation. Secondary inorganic aerosol constituents (ammonium, nitrate, sulfate) are primary drivers of PM2.5-associated polycythemia. Clinical complications include hyperviscosity (hematocrit >45%), thrombotic events (43% increased venous thromboembolism risk with PM2.5. Preventive interventions range from source-level emission controls to individual-level personal protective equipment (facemasks, HEPA air purifiers) and clinical phlebotomy.
Conclusion: Air pollution drives secondary polycythemia via hypoxia-EPO pathways integrated with oxidative stress and systemic inflammation. Evidence supports urgent clinical vigilance in high-exposure populations and multisectoral public health action targeting emission reduction, population surveillance, and individual protection.