Circulating Platelet-Neutrophil Aggregates as Novel Biomarker for Coagulopathy Diagnosis and Disseminated...

Platelet-leukocyte aggregates (PLAs) drive immunothrombosis by promoting leukocyte activation and tissue factor release in sepsis. However, their utility as early predictors of sepsis-induced coagulopathy (SIC) and disseminated intravascular coagulation (DIC) remains unestablished. This study aimed to develop and validate a PLA-based model for SIC diagnosis and DIC prediction.

A prospective prediction study was conducted with 101 sepsis patients in Beijing Jishuitan Hospital between May 2024 and May 2025. Percentage and mean fluorescence intensity (MFI) of different subtypes of PLAs were measured by flow cytometry. Receiver operating characteristic (ROC) curves and Cox regression were performed, assessing the performance of PLAs to diagnose SIC and predict DIC.

Platelet-neutrophil aggregate MFI (PNA-MFI) demonstrated excellent diagnostic accuracy for SIC (p < 0.001, AUC = 0.789, 95% CI: 0.699-0.880, cut-off value = 2797, sensitivity = 76.2%, specificity = 78.0%, negative predictive value (NPV) = 83.9%, and positive predictive value (PPV) = 68.8%) and superior DIC prediction (p < 0.001, AUC = 0.781, 95% CI: 0.680-0.883, cut-off value = 2621, sensitivity = 83.3%, specificity = 64.9%, NPV = 92.6%, and PPV = 42.6%). Kaplan-Meier analysis showed that high PNA-MFI patients (PNA-MFI ≥ 2621) were more likely to develop DIC (log-rank p  < 0.001, hazard ratio: 6.80 [high PNA-MFI/low PNA-MFI], and 95% CI:2.97-15.61).

PNA-MFI is a promising biomarker for SIC diagnosis and DIC prediction. While internally validated, external validation is essential prior to clinical implementation, and further multicenter studies are warranted to definitively establish its clinical value.