The pathogenesis of thrombosis in patients with polycythemia vera (PV) results from a complex interplay of patient-and disease-related variables. According to age and previous thrombosis, patients are traditionally stratified as “high risk” or “low risk.” However, recently, novel disease-related determinants such as leukocyte (white blood cell [WBC]) levels and JAK2V617F mutational burden have been proposed as new contributing predictors of vascular events and are now under active investigation. 1 In the largest epidemiologic study (European Collaboration on Low-dose Aspirin), baseline leukocytosis emerged as an independent risk factor of arterial thrombosis, 2 and since then, no confirmatory data have been produced. The Italian randomized trial Cytoreductive Therapy in Polycythemia Vera (CYTO-PV) tested different intensities of cytoreductive therapy (phlebotomy and cytoreductive drugs) to prevent thrombotic events and showed that the arm maintained at hematocrit (HCT) target, 45% had a significant 4 times lower rate of cardiovascular death and major thrombosis than did the arm with a HCT target of 45% to 50%. Analysis also showed that during the follow-up, patients in the high-HCT group had significantly higher WBC counts than did those in the low-HCT group. 3 As expected, the intensity of therapy (phlebotomy and hydroxyurea) was higher in the low-HCT than in high-HCT arm. 3 During the follow-up (median, 28.9 6 10.9 months), the median HCT level in the low-HCT group was 44.4% compared with 47.5% in the high-HCT group. Fatal and nonfatal cardiovascular events were registered in 28 patients (7.7%), corresponding to an incidence rate of 3.4 per 100 person-years. Platelet levels did not differ in the 2 arms, whereas WBC count persisted at significantly higher levels in the high-HCT group than in the low-HCT group (P,. 001). To discern the relative merits of more stringent HCT control from the role of a lower WBC count to reduce the cardiovascular events, we carried out a multivariable time-dependent analysis4 by considering the level of WBC categorized into approximate quartiles and recorded in the last clinical visit before the thrombotic event. The study was approved by each Institutional Review Board. Results indicate that the risk of thrombosis was clearly increased in patients with WBC count. 7 3 109/L, becoming statistically significant when WBC count was. 11 3 109/L (Table 1).