Ferritin-to-Platelet Ratio Predicts Dengue Shock and Ferritin/ALT Ratio Discriminates Severe Hepatitis: Novel Composite Indices from a Prospective Serial Biomarker Study 

<title>Abstract</title> <p>Background Dengue fever poses a major public health challenge in India, with early prediction of severe complications—particularly dengue shock syndrome and severe hepatitis—remaining an unmet clinical need. Serum ferritin, an acute-phase reactant of macrophage activation, shows promise as a severity biomarker; however, serial kinetic data and novel ferritin-derived composite indices have not been systematically evaluated in adult Indian populations. This study aimed to characterise serial ferritin kinetics and to derive and evaluate the Ferritin-to-Platelet Ratio (FPR) and the Ferritin/ALT Ratio (FLR) as novel triage indices for dengue shock and severe hepatitis respectively. Methods A prospective observational study enrolled 100 adult dengue patients (WHO 2009 confirmed) at SMIMER, Surat, between June 2020 and November 2021. Serum ferritin was measured by sandwich ELISA on Days 1, 3, and 5 of hospitalisation. Severity was classified as non-severe (n = 72) or severe (n = 28). Non-circular primary endpoints—shock/DSS (n = 22), severe thrombocytopenia (&lt; 20,000/µL; n = 27), and severe hepatitis (AST/ALT ≥ 1,000 IU/L; n = 18)—were used for diagnostic accuracy analyses. FPR (ferritin ÷ platelet count) and FLR (ferritin ÷ ALT) were pre-specified composite indices. Results Ferritin followed a rise-peak-fall trajectory peaking on Day 3 (mean 955 ± 177 ng/ml; Friedman χ²=142.27, p &lt; 10⁻¹⁶). FPR Day 1 achieved AUC 0.913 (95% CI 0.858–0.969) against composite severity, with severe patients showing an eight-fold higher median FPR than non-severe patients (56.0 vs 7.3; p &lt; 0.001). FLR Day 1 discriminated severe hepatitis with AUC 0.995 (95% CI 0.988–1.000), reflecting the disproportionate ALT surge collapsing the ratio in hepatocellular injury (severe hepatitis median FLR 0.30 vs non-hepatitis 8.43; p &lt; 0.001). Against non-circular outcomes, Ferritin Day 1 predicted shock/DSS with AUC 0.789 (0.666–0.912) and severe thrombocytopenia with AUC 0.727 (0.606–0.848). The ferritin-platelet inverse correlation was robust and demographic-independent (partial Spearman rho = − 0.392; p &lt; 0.001). Ferritin provided no incremental benefit over platelet count alone (NRI = 0.143, 95% CI − 0.167 to 0.236; IDI = 0.000). Conclusions The Ferritin-to-Platelet Ratio is a novel, cost-free composite index predicting dengue shock with AUC 0.913, and the Ferritin/ALT Ratio discriminates severe hepatitis with near-perfect accuracy (AUC 0.995). Both indices warrant prospective multi-centre validation as bedside triage tools in dengue-endemic settings. Clinical Trial registration Not applicable.</p>