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

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.