MPN-103 A Real-World Evaluation of the Association Between Elevated Blood Counts and Thrombotic Events in Polycythemia Vera: Analysis of Data From the REVEAL Study

Context: Polycythemia Vera (PV) leads to elevated peripheral blood counts (PBCs) and increased thromboembolic events (TE) risk. The conventional model used to determine TE-risk and treatment strategy includes advanced age and TE-history. Association between TE-risk and elevated hematocrit (HCT) is established; association with white-blood-cell count (WBC) or platelet count (PLT) have not been assessed consistently. Objective: Evaluate association between elevated PBCs and TE-risk. Design: Real-world Prospective Observational Study of Patients with Polycythemia Vera in US Clinical Practices (REVEAL; NCT02252159). Setting: Clinical practice. Patients: Included: ≥3 post-enrollment PBCs; excluded: post-enrollment TE without PBCs <6 months before that TE. Interventions: Noninterventional. Main Outcome Measures: Association was assessed by the time-dependent covariate Cox-proportional hazards model. Time-to-first post-enrollment TE was modeled; for patients with no TE, time was censored at last visit. Each lab parameter was individually modeled with sex, age, disease duration, and TE-history at enrollment (baseline covariates) and treatment (time-dependent covariates). Thresholds included: HCT>45%, WBC>11×10⁹/L, PLT>400×10⁹/L. Alternative thresholds included: WBC<7, ≥7–<8.5; ≥8.5–<11, ≥11×10⁹/L, WBC>12×10⁹/L with controlled HCT≤45%, and PLT>600×10⁹/L. Results: Of 2510 enrolled, 2271 patients were included: median age, 67 years (range, 22–95); male, 54.1%; median disease duration, 4.1 years (range, 0–56.3), TE-history, 20.1%; receiving hydroxyurea, 52.6%; TEs, 4.7% (arterial, 1.3%; venous, 3.3%). HCT>45% vs ≤45% (HR=1.84 [95% CI, 1.234–2.749], P=0.0028), WBC>11 vs ≤11×10⁹/L (HR=2.35 [1.598–3.465], P<0.0001), and PLT>400 vs ≤400×10⁹/L (HR=1.60 [1.088–2.359], P=0.0170) were each associated with significantly increased TE-risk. WBC≥ 11 vs <7×10⁹/L was associated with the highest TE-risk (HR=2.61 [1.594–4.262], P=0.0001). TE-risk was increased for PLT>600 vs ≤600×10⁹/L, but not significantly (HR=1.37 [0.763–2.468], P=0.2913). WBC>12 vs ≤ 12×10⁹/L was significantly associated with increased TE-risk at HCT≤45% (HR=1.95 [1.066–3.554], P=0.0300). In all models, advanced age, female sex, and TE-history were associated with increased TE-risk. Conclusions: The results demonstrate significant associations individually between elevated HCT, PLT, WBC (>11 and?>12×10⁹/L), and increased TE-risk. Elevated WBC (>12×10⁹/L) is significantly associated with increased TE-risk when HCT is controlled, indicating that TE-risk may be reduced by controlling WBC as well as HCT. These data support incorporation of PBCs into risk stratification and treatment strategies for PV patients.