Sepsis: network pathophysiology and implications for early diagnosis

Sepsis, a medical emergency, is the overwhelming host response to infection leading to organ failure. The pathophysiology of this heterogeneous disease includes an inflammatory response that stimulates a complex interaction between endothelial and complements with associated coagulation abnormalities. Despite a more comprehensive understanding of sepsis pathophysiol-ogy, there exists a translational gap to improve sepsis diagnosis clinically. Many of the proposed biomarkers to diagnose sepsis lack sufficient specificity and sensitivity to be used in routine clinical practice. There has also been a lack of progress in diagnos-tic tools due to the focus on the inflammatory pathway. Inflammation and coagulation are known to be linked to the innate immune response. Early immunothrombotic changes could result in the early switch from infection to sepsis and aid in sepsis di-agnosis. This review integrates both preclinical and clinical studies that highlight sepsis pathophysiology providing a framework for how the development of immunothrombosis could be used as a starting point to investigate biomarkers for early sepsis diagnosis.

Automated summary

Sepsis is an overwhelming host response to infection, which leads to organ failure. The pathophysiology involves inflammation, endothelial interactions, complement activation, and coagulation abnormalities. The current biomarkers for diagnosing sepsis lack specificity and sensitivity. This review proposes exploring early immunothrombosis as a potential starting point for investigating biomarkers for early sepsis diagnosis.