Real-world thrombotic outcomes in patients with secondary erythrocytosis in comparison with polycythemia vera

Key points 1. A real-world cohort of patients with secondary erythrocytosis had higher rates of thrombosis compared to treated polycythemia vera. 2. Secondary erythrocytosis was associated with higher prevalence of smoking, obesity, and diabetes mellitus. Secondary erythrocytosis is a common finding in hematology clinics, yet its clinical outcomes, particularly rates of arterial and venous thrombosis, remain poorly defined. We conducted a retrospective study to characterize this referral population and evaluate thrombotic outcomes. Adults with erythrocytosis (hemoglobin >160 g/L in females, >165 g/L in males) who underwent molecular testing between 2018-2023 and were not diagnosed with a myeloproliferative neoplasm or other hematologic malignancy were included. For comparison, we identified adults diagnosed with polycythemia vera (PV) during the same period. 581 patients with secondary erythrocytosis and 103 with PV were included. The most prevalent risk factors for secondary erythrocytosis were smoking, obstructive sleep apnea, hypoxic lung diseases, and medications. Following diagnosis, incidence of arterial and venous thrombosis in patients with secondary erythrocytosis was 1.89 events and 0.95 events per 100 patient-years, respectively, with a combined thrombosis rate of 2.71 events per 100 patient-years. These rates were significantly higher than those observed following a diagnosis of PV. Possible explanations for higher thrombosis rates in the secondary erythrocytosis group include higher burden of cardiovascular risk factors (smoking, obesity, diabetes), and greater use of standard-of-care therapies such as antiplatelet agents and cytoreduction in the PV group. These findings suggest that patients with secondary erythrocytosis may have higher thrombotic risk compared to a treated PV cohort, underscoring the need for further research to clarify risk factors and guide management for this complex and heterogeneous population.