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

Area of Science:

• Genetics and Medicine
• Hematology
• Infectious Diseases

Background:

• Sepsis involves a dysregulated host response to infection, often accompanied by platelet abnormalities.
• The precise causal role of platelets in sepsis pathogenesis and outcomes remains incompletely understood.

Purpose of the Study:

• To investigate the causal relationship between platelet traits and sepsis risk using a bidirectional Mendelian randomization approach.
• To explore the reverse causality: the impact of sepsis on platelet count, platelet crit, mean platelet volume, and platelet distribution width.

Main Methods:

• A two-sample Mendelian randomization (MR) study utilized genetic variants from large genome-wide association studies as instrumental variables.
• MR analysis assessed the causal effects of platelet count (PLT), platelet crit (PCT), mean platelet volume (MPV), and platelet distribution width (PDW) on sepsis risk and prognosis.
• Sensitivity analyses and heterogeneity tests were performed to ensure result validity and robustness.

Main Results:

• Genetically predicted lower platelet crit (PCT) and mean platelet volume (MPV) were associated with an increased risk of developing sepsis.
• In the reverse analysis, decreased platelet count (PLT) was significantly associated with 28-day sepsis mortality, indicating a link to poor prognosis.
• No significant causal links were found between sepsis and other investigated platelet traits (PDW).

Conclusions:

• This study provides novel evidence suggesting that low PCT and MPV causally increase sepsis risk.
• Decreased PLT is causally linked to sepsis with a poor prognosis, underscoring the prognostic significance of platelet count.
• The findings highlight specific platelet parameters as potential causal factors in sepsis development and mortality.