Mapping and tracking inflammatory platelets and their extracellular vesicles to improve sepsis outcomes

This research project was awarded the 2024 Birmingham BRC Collaboration Fund

Status: Project complete

Sepsis is a life-threatening condition that arises when the body’s response to infection causes injury to its own tissues and organs. Patients with sepsis are at risk of developing acute respiratory distress syndrome (ARDS), which significantly increases mortality. Despite significant advances in patient care, there remain no effective targeted treatments for sepsis, highlighting the need for a better understanding of the underlying disease mechanisms.

Project aims

This project aimed to understand the role of a specific type of a blood cell, called platelet, and their extracellular vesicles (small particles released from cells) in sepsis. These new insights could lead to new treatments that improve outcomes for patients with this serious condition.

Our researchers identified a previously unrecognised subgroup of hyperinflammatory platelets in patients with sepsis and COVID-19, with higher levels linked to more severe disease. These platelets not only contribute directly to inflammation and abnormal clotting but also release tiny particles called extracellular vesicles, which can spread inflammatory signals throughout the body.

Using advanced proteomic techniques, the team analysed the molecular composition of these extracellular vesicles in patients with ARDS compared with controls, identifying key therapeutic targets.

The research also uncovered a mechanism by which systemic inflammation drives the formation of these hyperinflammatory platelets, causing a subset of platelets to adopt immune-like characteristics and enter a highly inflammatory state.

Importantly, the findings suggest that the harmful inflammatory functions of platelets can potentially be separated from their essential role in preventing bleeding. This raises the possibility of developing new therapies that selectively target the damaging effects of platelets in sepsis without increasing bleeding risk.