Elevated White Blood Cell Levels and Thrombotic Events in Patients With Polycythemia Vera: A Real-World Analysis of Veterans Health Administration Data

Abstract

Patients with polycythemia vera (PV) have a substantial risk of thrombotic events (TEs). In the present retrospective analysis using Veterans Health Administration claims data, 25% of 1565 patients experienced a TE during follow-up. We observed a positive, significant association between white blood cell (WBC) counts ‡ 8.5 3 10 9 /L and TE occurrence (reference, WBC count < 7.0 3 10 9 /L), supporting continued inclusion of WBC count control in disease management. Background: Patients with polycythemia vera (PV) have a substantial risk of thrombotic events (TEs). The objective of the present analysis was to describe the association between white blood cell (WBC) levels and occurrence of TEs among patients with PV from a large real-world population. Patients and Methods: The present retrospective analysis using Veterans Health Administration claims data (October 1, 2005, to September 30, 2012) evaluated adult patients assigned to 4 WBC count categories (WBC count < 7.0, 7.0-8.4, 8.5 to < 11.0, and ! 11.0 Â 10 9 /L) to compare the risk of TEs (reference, WBC count, < 7.0 Â 10 9 /L group). Analysis was performed using a Cox proportional hazards model, considering WBC status as a time-dependent covariate. Results: Of the 1565 patients with PV included in the present analysis, the WBC count was < 7.0 Â 10 9 /L for 428 (27.3%), 7.0 to 8.4 Â 10 9 /L for 375 (24.0%), 8.5 to < 11.0 Â 10 9 /L for 284 (18.1%), and ! 11.0 Â 10 9 /L for 478 (30.5%). Of the 1565 patients, 390 (24.9%) had experienced a TE during the study period. The mean follow-up ranged from 3.6 to 4.5 years. Compared with the reference group (WBC count < 7.0 Â10 9 /L), the hazard ratio for TEs was 1.10 (95% confidence interval [CI], 0.82-1.48; P ¼ .5395), 1.47 (95% CI, 1.10-1.96; P ¼ .0097), and 1.87 (95% CI, 1.44-2.43; P < .0001) for patients with a WBC count of 7.0 to 8.4, 8.5 to < 11.0, and ! 11.0 Â10 9 /L, respectively. Conclusion: A positive, significant association between an increased WBC count of ! 8.5 Â10 9 /L and the occurrence of TEs was observed in patients with PV. The potential thrombogenic role of WBCs in patients with PV supports the continued inclusion of WBC count control in disease management and evaluation of the response to therapy.

Updates in the management of polycythemia vera and essential thrombocythemia

“…24 A very similar analysis of a cohort of 1565 patients with PV from US Veterans Affairs hospitals demonstrated that patients with leukocyte counts ⩾8.5–<11 × 10 9 /l had a significantly increased risk of thrombotic events compared with those with leukocytes <7 × 10 9 /l, with the hazard ratio highest for those with leukocyte counts ⩾11 × 10 9 /l. 25 Similar findings were also reported in a time-dependent analysis of the ECLAP (European Collaboration on Low-Dose Aspirin in Polycythemia Vera) study which found, after adjusting for potential confounding factors, that patients with leukocyte counts >15 × 10 9 /l had a significantly higher risk of thrombosis compared with those with leukocyte counts <10 × 10 9 /l. 26 Consensus guidelines from the National Comprehensive Cancer Network (NCCN) in the US recognize progressive leukocytosis, along with new thrombosis or disease-related major bleeding, progressive disease-related symptoms, a frequent or persistent need for phlebotomy with poor tolerance of the same, symptomatic or progressive splenomegaly and symptomatic thrombocytosis as potential indications for initiation of cytoreductive therapy in ‘low-risk’ patients with PV.…”

Hematocrit, White Blood Cells, and Thrombotic Events in the Veteran Population With Polycythemia Vera

“…Two recently published retrospective analyses from Parasuraman and colleagues used data from the Veterans Health Administration (VHA), the largest integrated health care system in the US, with an aim to replicate findings from CYTO-PV in a real-world population. 16,17 The 2 analyses focused independently on the effects of Hct control and WBC count on the risk of a thrombotic event in patients with PV.…”

“…In the second analysis, the authors investigated the relationship between WBC counts and thrombotic events. 16 Evaluable patients (N = 1565) were grouped into 1 of 4 cohorts based on the last WBC measurement taken during the study period before a thrombotic event or through the end of follow-up: (1) WBC < 7.0 × 10 9 /L, (2) 7.0 to 8.4 × 10 9 /L, (3) 8.5 to < 11.0 × 10 9 /L, or (4) ≥ 11.0 × 10 9 /L. Mean follow-up time ranged from 3.6 to 4.5 years among WBC count cohorts, during which 24.9% of patients experienced a thrombotic event.…”

“…Compared with the reference cohort (WBC < 7.0 × 10 9 /L), a signifi-cant positive association between WBC counts and thrombotic event occurrence was observed among patients with WBC counts of 8.5 to < 11.0 × 10 9 /L (HR, 1.47; 95% CI, 1.10-1.96; P < .01) and ≥ 11 × 10 9 /L (HR, 1.87; 95% CI, 1.44-2.43; P < .001) (Figure 2). 16 When including all patients in a sensitivity analysis regardless of whether they experienced thrombotic events before the index date (N = 1876), similar results were obtained (7.0-8.4 × 10 9 /L group: HR, 1.22; 95% CI, 0.97-1.55; P = .0959; 8.5 -11.0 × 10 9 /L group: HR, 1.41; 95% CI, 1.10-1.81; P = .0062; ≥ 11.0 × 10 9 /L group: HR, 1.53; 95% CI, 1.23-1.91; P < .001; compared with < 7.0 × 10 9 /L reference group). Rates of phlebotomy and cytoreductive treatments were similar across groups.…”

“…Rates of phlebotomy and cytoreductive treatments were similar across groups. 16 Some limitations to these studies are attributable to their retrospective design, reliance on health records, and the VHA population characteristics, which differ from the general population. For example, in this analysis, patients with PV in the VHA population had significantly increased risk of thrombotic events, even at a lower WBC count threshold (≥ 8.5 × 10 9 /L) compared with those reported in CYTO-PV (≥ 11 × 10 9 /L).…”