Complement-Coagulation Axis and Metabolic Dysregulation Underlie the Transition from Mild to Severe Heat Stroke: A...

Heat stroke is a life-threatening condition marked by hyperthermia, central nervous system dysfunction, and multiorgan injury. Exertional heatstroke (EHS) primarily affects healthy young individuals after intense training or heavy labor in hot, humid environments. However, the molecular events driving the progression from mild to severe EHS remain poorly understood. This study integrated clinical data with serum proteomics to identify key pathways and biomarkers involved in EHS progression.

Serum samples were collected from mild EHS patients (n=7), severe EHS patients (n=7), and controls. Demographic data, laboratory results, and Sequential Organ Failure Assessment scores were recorded. Serum proteins were analyzed using label-free mass spectrometry. Comparisons between mild versus control, severe versus control, and severe versus mild groups. Differentially expressed proteins were identified and analyzed using bioinformatics techniques. Enzyme-linked immunosorbent assay was used for further validation.

Comparison of clinical data between mild and severe cases exhibited significantly higher markers of inflammation (white blood cell), coagulation abnormalities, organ injury and higher Sequential Organ Failure Assessment scores.Proteomic analysis identified 51 differentiall expressed proteins, highlighting activation of the complement-coagulation axis, nuclear factor kappa-B signaling, metabolic dysregulation, and immune responses. Von Willebrand factor, Mannan-binding lectin serine protease 1, coagulation factor VIII, and vitamin K-dependent protein C exhibited strong discriminative ability and correlated with severity. HSP70/HSP90 levels were elevated in EHS but not severity-dependent.

These findings indicate complement- coagalation and metabolic dysregulation drive mild to severe EHS progression, with identified proteins serving as potential biomarkers and therapeutic targets.