PLATELET TRAITS AND SEPSIS RISK AND PROGNOSIS: A BIDIRECTIONAL TWO-SAMPLE MENDELIAN RANDOMIZATION STUDY

ABSTRACT Background: Sepsis is a critical medical condition characterized by a dysregulated host response to infection. Platelet abnormalities frequently manifest in sepsis patients, but the causal role of platelets in sepsis remains unclear. This study employed a bidirectional two-sample Mendelian randomization (MR) approach to investigate the causal direction between platelets and sepsis. Methods: MR analysis was used to investigate the causal effect of four platelet traits—platelet count (PLT), platelet crit (PCT), mean platelet volume (MPV), and platelet distribution width (PDW)—on sepsis risk and prognosis. Additionally, the study explored the reverse causality, assessing the impact of sepsis on these platelet traits. Genetic variants from large-scale genome-wide association studies served as instrumental variables to infer causality. Sensitivity analyses and heterogeneity tests were conducted to ensure the validity and robustness of the results. Results: Genetically predicted decreased PCT (OR = 0.938, P = 0.044) and MPV (OR = 0.410, P = 0.006) were associated with an increased risk of sepsis. In the reverse direction, 28-day sepsis mortality was significantly associated with decreased PLT (OR = 0.986, P = 0.034). No significant causal relationships were observed between sepsis and other platelet traits. Conclusions: This study suggests a causal association between low PCT and MPV levels and increased risk of sepsis. Additionally, sepsis with a poor prognosis was causally linked to decreased PLT. These findings provide novel evidence for the causal relationship between platelet traits and sepsis.