Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by clonal proliferation of hematopoietic progenitor cells, and is associated with an increased risk of thrombotic events (TEs). Established risk factors for TEs in patients with PV include advanced age, TE history, and elevated hematocrit. Whereas an association of TE with elevated white blood cell (WBC) counts has been suggested by retrospective studies, this relationship needs further validation. The pRospective obsErvational study of patients with polycythemia VEra in US clinicAL practices (REVEAL) collected prospective clinical data from 2510 patients with PV with a median (range) follow up of 44.7 (2-59) months from enrollment. Using time-dependent covariate Cox proportional hazards models, blood counts were individually modeled with sex, age, disease duration, TE history at enrollment (baseline covariates) and treatment (time-dependent covariate). Analysis of 2271 participants identified 142 TEs in 106 patients. Significant associations with initial TE occurrence during the study period were observed for hematocrit >45% (hazard ratio (HR) = 1.84; [95% confidence interval, 1.234-2.749], P = .0028) and WBC >11×109/L (HR = 2.35 [1.598-3.465], P < .0001) . Elevated WBC count was significantly associated with initial TE occurrence in both low-risk and high-risk PV. When hematocrit was controlled at ≤45%, WBC >12×109/L was significantly associated with TE occurrence (HR = 1.95 [1.066-3.554], P = .0300). The results support incorporation of WBC count into PV risk-stratification and studies of treatment strategies, and indicate the importance of controlling both hematocrit and WBC count in disease management. This trial is registered at www.clinicaltrials.gov as #NCT02252159. -