Aaron T. Gerds, MD, MS, Associate Professor of Medicine, Deputy Director for Clinical Research at the Cleveland Clinic Taussig Cancer Institute and Medical Director of the Case Comprehensive Cancer Center Clinical Research Office at Cleveland Clinic. In this audio, he speaks about the EHA 2022 abstract A Real-World Evaluation of the Association Between Elevated Blood Counts and Thrombotic Events in Polycythemia Vera: An Analysis of Data from the REVEAL Study.
Outline
Back story
PV is characterized by clonal hematopoiesis, which results in higher peripheral blood counts and an increased risk of thrombotic events (TEs). The standard risk model used to predict TE risk/treatment strategy includes advanced age and TE history. Although there are connections between TEs and higher hematocrit (HCT) levels, relationships with white blood cell (WBC) or platelet (PLT) counts have not been systematically examined. The large, prospective Observational Study of Patients with Polycythemia Vera in US Clinical Practices (REVEAL; NCT02252159) monitored patients with PV treated in community or academic facilities.
Targets
Using REVEAL data, this study looked at the links between high blood counts and TEs in patients with PV.
Methodology
Eligible patients had three lab values (blood counts) after enrollment; patients having a post-enrollment TE but no lab value six months earlier were excluded. A time-dependent covariate Cox proportional hazards model was used to examine the relationship between blood counts and TEs. Time to first post-enrollment TE was modeled, with time censored at last known visit for patients who did not have TE. Each lab parameter was modeled with gender, age, disease duration, and TE history as baseline factors and therapy as a time-dependent covariate. Blood counts were included as binary time–dependent covariates if HCT was greater than 45 percent, WBC was greater than 11109/L, and PLT was greater than 400109/L. To determine lab values between observed lab values, linear interpolation was applied. Alternative WBC thresholds (7, 7 to 8.5; 8.5 to 11, and 11109/L, and >12109/L with HCT regulated at 45%) and PLT counts (>600109/L) were tested. P0.05 was used to determine statistical significance.
Outcomes
There were 2271/2510 eligible points (median age, 66 years [range, 22–95]; male, 54.1 percent). The median disease duration was 4.1 years (range, 0–56.3), 456 patients (20.1 percent) had a history of TE, and 52.6 percent got hydroxyurea. Thirty patients experienced arterial TEs (the most common being transient ischemic attack [n=15]) and 76 had venous TEs (the most common being deep vein thrombosis [n=37]).
Elevated HCT levels (>45 percent, HR=1.84 [95 percent CI, 1.234–2.749], P=0.0028), WBC (>11109/L, HR=2.35 [1.598–3.465], P=0.0001), and PLT counts (>400109/L, HR=1.60 [1.088–2.359], P=0.0170) were all linked to an elevated risk of TE (Table 1). When compared to WBC count 7109/L, WBC count 11109/L is related with the highest TE risk (HR=2.61 [95 percent CI, 1.594–4.262], P0.0001). With HCT managed at 45 percent, elevated WBC >12109/L was strongly related with higher risk of TE. PLT count greater than 600109/L increased TE risk (HR=1.37 [95 percent CI, 0.763–2.468]) compared to PLT count less than 600109/L, however this was not statistically significant (P>0.05). Advanced age, female sex, and TE history were all linked with higher TE risk in all models.
Conclusions
This study of REVEAL, the largest real-world cohort of PV patients to date, found that higher HCT levels (>45 percent), WBC counts (>11109/L), and PLT counts (>400109/L) were related with an increased risk of TE. When HCT was decreased, a relationship of raised WBC >12109/L with increased risk of TE was also detected, demonstrating that TE risk may be lowered by controlling WBC as well as HCT. These findings suggest the necessity to incorporate blood count into risk categorization and treatment methods for patients with PV in clinical practice, as well as to go beyond the traditional risk model. More research is needed to understand the link between high blood counts and TEs.