Serum Bilirubin Levels and Risk of Venous Thromboembolism among Influenza Patients: A Cohort Study

Abstract

Objective This study aimed to investigate the associations between total serum bilirubin levels and the incidence of venous thromboembolism (VTE) among patients with influenza infection. Methods A retrospective cohort study was conducted among outpatients with laboratory-confirmed influenza using data from the Veterans Affairs Informatics and Computing Infrastructure (VINCI). Propensity score weighting was applied to balance study groups across baseline covariates. Cox proportional hazards models assessed VTE risk by total bilirubin levels, adjusting for important covariates including age, sex, race, comorbidity index, BMI, and smoking status. Results A total of 487 patients with total bilirubin levels <0.3 mg/dL, 8608 patients with levels between 0.3–1 mg/dL, and 1148 patients with levels >1 mg/dL were included. Patients with bilirubin <0.3 mg/dL exhibited a 6-fold higher risk of VTE compared to those with levels 0.3–1 mg/dL within 30 days of infection (HR = 6.2, 95% CI = 1.46–26.42). Elevated risks were noted through 90 days post infection (HR = 4.71, 95% CI = (1.42–15.67)) Conclusions Serum bilirubin levels, particularly below 0.3 mg/dL, were significantly associated with an increased risk of VTE among individuals with influenza. These findings suggest that lower bilirubin levels may contribute to heightened inflammatory responses and subsequent thromboembolic events in patients with influenza. The underlying mechanisms and potential therapeutic implications for VTE prevention among patients with acute respiratory infection warrants further consideration.