Link Between Elevated WBC and Thrombotic Events in Polycythemia Vera Highlights Potential Prevention Strategy

Patients with polycythemia vera (PV) who have controlled hematocrit (HCT) levels, but elevated white blood counts (WBC) are at an increased risk of thrombotic events (TEs), according to a presentation of the REVEAL study (NCT02252159) at the 2021 ASH Annual Meeting. The findings suggest that by controlling WBC in patients with PV, the risk of TEs may also be controlled.

Specifically, findings from the REVEAL study demonstrated that an elevated WBC count of >11 10⁹/L at HCT levels greater than 45% increased risk of TE (HR, 1.81; 95% CI, 0.993-3.301; P = .0526). An elevated WBC count of greater than 12 10⁹/L also increased risk of TE (HR, 1.95; 95% CI, 1.066-3.554; P=.0300). Other covariates observed in the analysis were consistent with previously demonstrated trends.

“PV in particular is associated with thrombotic risk,” explained Aaron Gerds, MD, MS, of Cleveland Clinic Taussig Cancer Institute, in a presentation of the findings. “[In] this particular analysis we look[ed] to evaluate the association between elevated blood counts and occurrence of thrombotic events in patients with polycythemia vera using this REVEAL database.”

The REVEAL study is a multicenter, noninterventional, prospective observational study, which enrolled patients with PV from US community practice and academic centers. Key inclusion for this trial included a clinical diagnosis of PV per physician judgement. Patients also needed to be under physician supervision for management of PV and older than 18 years of age.

Exclusion criteria included a life expectancy of under 6 months, a history of allogeneic hematopoietic cell transplantation or a plan to receive this treatment, or history of splenectomy. Enrolled patients need to have at least 3 laboratory blood count values post enrollment. In addition, patients who developed TE following enrollment but did not have laboratory values within 6 months of TE enrollment were not included.

Researchers collected data at diagnosis, at a 6-month period, and during follow-up 3 years from last patient enrollment. The data collection period was between July 2014 and August 2019.

Association Between Blood Counts and TEs

The main study threshold was to determine the association between blood counts and TEs.

For patients with elevated HCT and TEs, main observed associations included age (HR, 1.03; 95% CI, 1.010-1.046; P = .0026), male sex (HR, 0.54; 95% CI, 0.362-0.799; P = .0021), history of TE (HR, 2.49; 95% CI, 1.667-3.717; P < .0001), and HCT greater than 45% vs <45% (HR, 1.84; 95% CI, 1.234-2.749; P = .0028).

Similar associations were linked with elevated WBC and PLT counts (>400 x 109/L). In regard to WBC, there was an increased risk for age (HR, 1.02; 95% CI, 1.007-1.042; P = .0068), male sex (HR, 0.58; 95% CI, 0.393-0.858, P = .0063), history of TE (HR, 2.42; 95% CI, 1.623-3.619; P < .0001), and HCT >45% vs <45% (HR, 2.35;95% CI, 1.598-3.465; P < .0001).

Regarding increased PLT counts, there was an increased risk for age (HR, 1.03; 95% CI, 1.010-1.046; P = .0022), male sex (HR, 0.62; 95% CI, 0.416-0.914; P = .0162), history of TE (HR, 2.45; 95% CI, 1.640-3.654; P <.0001), and HCT >45% vs <45% was (HR, 1.60; 95% CI, 1.088-2.359; P = .0170).

Post-Enrollment Thrombotic Events

A total of 104 (4.7%) of 2271 enrolled patients experienced a post-enrollment thrombotic event. Thirty of these patients experienced an arterial TE event, and 76 experienced a venous TE event. The most common arterial TE event was transient ischemic attack (n = 5) and the most common venous TE event was deep vein thrombosis (n = 37).

Laboratory parameters were modeled with consideration for sex, age, disease duration, and TE status at time of enrollment as a baseline covariates and treatment history (either hydroxyurea or other PV treatments). At the end of follow-up laboratory test, blood counts were included a binary time-dependent covariates using the following thresholds: HCT greater than 45%, WBC greater than 11 x 10⁹/L, and PLT greater than 400 x 10⁹/L.

Researchers determined laboratory values including linear interpolation. Furthermore, researchers evaluated alternative thresholds with the following values: WBC (<7 x 10⁹/L >7) to (<8.5 x 10⁹/L, >8.5) to (<11 x 10⁹/L, >11 x 10⁹/L) and PLT (>600 x 10⁹/L).

Researchers used the Cox proportional hazards model to calculate hazard ratios (HRs) and P values; P values of <.05 were considered statistically significant. Except for WBC, PLT, and HCT, all covariates were measured at baseline.

“This analysis of the REVEAL study, which is the largest real-world cohort of patients with PV prospectively studied, demonstrated that there was an association between elevated blood counts and thrombotic events, particularly a white blood cell count over 11 in all patients,” Gerds concluded.

He added that “We should be moving beyond the conventional risk models, and start to include additional factors—whether we're talking about blood counts, allele burdens, even lymphocyte counts, perhaps—to make better models to predict thrombosis. Because thrombosis is associated with inferior outcomes overall in these populations, if we can make better models, we can intervene in higher-risk populations to improve their overall outcomes.”

Reference

Gerds A, Mesa R, Burke J, et al. A real-world evaluation of the association between elevated blood counts and thrombotic events in polycythemia vera (analysis of data from the REVEAL study). Presented at: 2021 ASH Annual Meeting and Exposition; December 11-14, 2021; Atlanta, GA. Abstract 239.