Predictive Performance of a Serum sRAGE/sVEGFR-3 Dual-Biomarker Combination for Hypercoagulability Status in Pediatric Mycoplasma pneumoniae Pneumonia: A Retrospective Cohort Analysis.

OBJECTIVE: To evaluate serum soluble receptor for advanced glycation end products (sRAGE) and soluble vascular endothelial growth factor receptor 3 (sVEGFR-3) as biomarkers for hypercoagulable state in children with Mycoplasma pneumoniae pneumonia (MPP). METHODS: We retrospectively enrolled 352 children with MPP (hypercoagulable, n=98; non-hypercoagulable, n=254). Serum sRAGE and sVEGFR-3 were measured by enzyme-linked immunosorbent assay (ELISA). Spearman analysis, Box-Tidwell test, and restricted cubic splines (RCS) assessed correlations/nonlinear effects; least absolute shrinkage and selection operator (LASSO) regression selected variables; multivariable logistic regression analyzed risk factors (variance inflation factor [VIF] for multicollinearity); receiver operating characteristic (ROC) curve analysis evaluated predictive value (Youden index cut-off); Bootstrap (1000 iterations) validated internally; net reclassification improvement (NRI) and integrated discrimination improvement (IDI) assessed incremental value. RESULTS: Serum sRAGE and sVEGFR-3 were elevated in the hypercoagulable group (both P<0.001), with shortened prothrombin time (PT), activated partial thromboplastin time (APTT), and elevated fibrinogen (FIB) and D-dimer (all P<0.05); both correlated negatively with PT/APTT and positively with FIB/D-dimer (all P<0.001). LASSO selected age, duration of fever, lactate dehydrogenase (LDH), Mycoplasma pneumoniae (MP) antibody titer, sRAGE, and sVEGFR-3 as candidate factors; duration of fever, MP antibody titer, sRAGE, and sVEGFR-3 were independent risk factors by multivariable logistic regression (all P<0.05; VIF<2). Single-marker areas under the curve (AUCs) were 0.840 (sRAGE) and 0.709 (sVEGFR-3); combined AUC was 0.870 (95% confidence interval [CI]: 0.831-0.909; sensitivity 86.61%, specificity 71.43%), outperforming single indicators (DeLong test, P<0.05), with optimism-corrected AUC 0.871 (95% CI: 0.863-0.875). Versus sRAGE and sVEGFR-3 alone, the combined model yielded NRI/IDI of 0.497/0.048 and 0.9719/0.2835, respectively (all P<0.001). CONCLUSION: Elevated serum sRAGE and sVEGFR-3 are associated with hypercoagulable state in children with MPP; combined detection may serve as an exploratory reference for early identification, but requires prospective longitudinal and independent multicenter validation for clinical translation.