Neutrophil-to-lymphocyte ratio is a novel predictor of venous thrombosis in polycythemia vera

Abstract

We investigated the neutrophil-to-lymphocyte ratio (NLR) as a predictor of thrombosis in polycythemia vera (PV). After a median follow-up of 2.51 years, of 1508 PV patients enrolled in the ECLAP study, 82 and 84 developed arterial and venous thrombosis, respectively. Absolute counts of total leukocytes, neutrophils, lymphocytes, platelets, and the NLR were tested by generalized additive models (GAM) to evaluate their trend in continuous scale of thrombotic risk. Only for venous thrombosis, we showed that baseline absolute neutrophil and lymphocyte counts were on average respectively higher (median: 6.8 × 10⁹/L, p = 0.002) and lower (median: 1.4 × 10⁹/L, p = 0.001), leading to increased NLR values (median: 5.1, p = 0.002). In multivariate analysis, the risk of venous thrombosis was independently associated with previous venous events (HR = 5.48, p ≤ 0.001) and NLR values ≥5 (HR = 2.13, p = 0.001). Moreover, the relative risk in both low- and high-standard risk groups was almost doubled in the presence of NLR ≥ 5. These findings were validated in two Italian independent external cohorts (Florence, n = 282 and Rome, n = 175) of contemporary PV patients. Our data support recent experimental work that venous thrombosis is controlled by innate immune cells and highlight that NLR is an inexpensive and easily accessible prognostic biomarker of venous thrombosis.

Fig. 1. Generalized additive proportional-hazard models (GAM) for arterial and venous thrombosis.

Generalized additive proportional-hazard models (GAM) for the prediction of arterial (A, B, C) and venous (D, E, F) thrombosis of absolute neutrophils, lymphocytes, and their ratio. The effect on the risk of arterial and venous thrombosis of neutrophils, lymphocytes, and their ratio is analyzed on a continuous scale by GAM smooth function with cubic splines. Hazard-ratio estimates (solid line) along with their 95% confidence intervals (gray area) are plotted in logarithmic scale.

Fig. 2. Venous thrombosis-free survival by NLR values.

Kaplan–Meier venous thrombosis-free survival estimates according to categories of NLR values (<5 or ≥5) in the learning cohort of ECLAP trial (overall [A] and stratified by standard risk categories [B]), and in two external validation cohorts of contemporary PV patients (Florence [C] and Rome [D]).