Reactive thrombocytosis in hospitalized pneumonia reflects intense inflammation and confers context-dependent mortality risk

Abstract Background Beyond hemostasis, platelets’ immune and inflammatory role is recognized and thrombocytosis is generally regarded as a marker of the inflammatory response. However, the immune functions of platelets remain beneath the surface, and previous studies have reported conflicting findings regarding the significance of thrombocytosis in infection-related diseases. Can reactive thrombocytosis be viewed as a “higher-is-worse or higher-is-better” predictor of clinical outcome? Methods We analyzed 2754 patients discharged from the respiratory and infectious-disease wards between 1 January 2021 and 11 June 2025, and patients from the MIMIC-IV 3.1 database were used as validation cohorts, grouped by peak platelet counts (< 90, ≥ 400, 90–399 × 10⁹/L). Cox regression and multivariate logistic regression were performed to analyze the relationship between platelet count and in-hospital mortality. Multivariate linear regression was used to analyze the relationship between platelet count and length of hospital stay (LOS). Results Patients with reactive thrombocytosis had longer hospital stays (13 vs. 10 days; p < 0.001) and higher inflammatory markers than those with normal platelet counts CRP (90.2 vs. 28.6 mg/L; p < 0.001), PCT (0.195 vs. 0.092 ng/mL; p < 0.001), WBC (12.6 vs. 8.4 × 10⁹/L; p < 0.001). Despite these differences, mortality (3.4% vs. 4.4%) did not differ, nor did the rates of bloodstream, fungal, or polymicrobial infections. Clustering analyses confirmed comparable overall microbial spectra between the two groups. The impact of thrombocytosis on mortality (HR, 0.52; 95% CI, 0.27–0.99; p = 0.047) is context-dependent: it trended toward higher mortality in non-septic patients (OR, 1.42; 95% CI, 0.64–2.86, p = 0.357) but toward lower mortality in those with sepsis (OR, 0.33; 95% CI, 0.05–1.51, p = 0.18). The same opposing pattern and the interaction of sepsis and thrombocytosis re-emerged (OR, 1.70; 95% CI, 0.95–2.92, p = 0.063 vs. OR, 0.58; 95% CI, 0.34–0.96, p = 0.04) in MIMIC-IV data. Thrombocytopenia is an independent risk factor for mortality (HR, 2.08; 95% CI, 1.48–2.93; p < 0.001) and has good combined predictive ability. Conclusions Thrombocytosis trended toward higher mortality in non-septic patients yet toward lower mortality in those with sepsis.