New research supports the incorporation of white blood cell (WBC) count into polycythemia vera (PV) risk-stratification for thrombosis. The findings by Aaron T. Gerds, MD, MS, associate professor of medicine at Cleveland Clinic in Ohio, and colleagues also indicate the importance of controlling both hematocrit and WBC count in disease management. They published the results of the REVEAL (pRospective obsErvational study of patients with polycythemia VEra in US clinicAL practices) trial, the largest prospective observational cohort of patients with PV, in Blood.
REVEAL included prospective clinical data from 2,510 patients with PV, and the median follow-up of 44.7 (range = 2-59) months from enrollment provided insights into both breadth and depth of disease. Dr. Gerds described REVEAL as an “incredibly large effort and incredibly important study.” He explained that he and his colleagues designed the study to determine whether clinicians can use basic parameters to better identify different risk factors for thrombotic events (TEs) in patients with PV. He said that clinicians currently use a “very antiquated and very simple” way of sorting patients into a high-risk or low-risk category based on age and history of blood clots.
The study found significant associations with initial TE occurrence for hematocrit greater than 45% (hazard ratio [HR] = 1.84, p=0.0028) and WBC count greater than 11 x 109/L (HR=2.35, p<0.0001). Although the authors acknowledged that one of the limitations of their study was the potential reporting bias of TEs introduced by subjectivity or misclassification associated with physician-reported events, they concluded that their data support the association between leukocytosis and TE risk. Their findings were also consistent with previous observations of hematocrit, advanced age, and history of TE as risk factors for TE.
When the investigators performed a subgroup analysis of patients with high-risk PV, they again found significant associations between hematocrit greater than 45% and WBC count of more than 11 x 109/L and increased TE risk. “Lots of patients will be on medicines to lower their platelet counts in PV,” Dr. Gerds said. In these patients, for whom hematocrit was controlled at 45% or higher, a WBC count greater than 12 x 109/L was significantly associated with TE occurrence (HR=1.95, p=0.0300).
Results from REVEAL thus indicate that, even if platelet counts are at target at hematocrit below 45%, an increase in WBCs is associated with a higher risk of blood clots. To some extent, this is not surprising, according to the researchers, given that activated WBCs express coagulation and fibrinolytic factors, as well as produce cytokines and other proteins that modulate normal coagulation hemostasis. The authors noted in their discussion, however, that the association of elevated absolute neutrophil count greater than 7 x 109/L with increased TE risk may provide further insights into the mechanism underlying the relationship between WBC and TE risk.
Additional subgroup analysis, this time by TE type, again identified WBC count as a shared risk factor and found additional distinct risk factors for venous compared with arterial TEs. What Dr. Gerds described as even more intriguing, however, was the discovery that “platelet counts did not have a linear relationship with blood clot risk.” Now that WBC count has been identified as a risk factor, future research will focus on whether decreasing WBC counts decreases the incidence of clots, Dr. Gerds said.
Any conflicts of interest declared by the authors can be found in the original article.
Reference
Gerds AT, Mesa R, Burke JM, et al. Association between elevated white blood cell counts and thrombotic events in polycythemia vera: analysis from REVEAL [published online ahead of print, 2023 Dec 24]. Blood. doi: 10.1182/blood.2023020232.
