Serum ferritin kinetics and ferritin-derived ratios in hospitalised adults with dengue: A prospective serial biomarker study
Year: 2026
Type: article
Study design: Observational Study
Abstract: Background Dengue causes major morbidity and mortality across India, where early identification of patients progressing to dengue shock syndrome or severe hepatitis remains an unmet need. Serum ferritin reflects macrophage activation, but its serial kinetics and ferritin-derived composite indices have not been rigorously evaluated in adult Indian populations. We characterised serial ferritin kinetics and evaluated two ferritin-derived ratios: the Ferritin-to-Platelet Ratio (FPR) and the Ferritin/ALT Ratio (FLR). Methodology This prospective observational study enrolled 100 adult WHO 2009-confirmed dengue patients at SMIMER, Surat (June 2020–November 2021). Serum ferritin was measured by sandwich ELISA on hospital Days 1, 3 and 5 and was also analysed by day of illness; platelet count and transaminases were the lowest and highest values recorded during the stay, and outcomes were recorded if present at any time between admission and discharge. Severity was classified as non-severe (n = 68) or severe (n = 32). Non-circular endpoints—shock/DSS (n = 22), severe thrombocytopenia <20,000/μL (n = 28), and severe hepatitis AST/ALT ≥ 1,000 IU/L (n = 18)—were the primary outcomes for diagnostic accuracy. FPR and FLR were pre-specified composite indices and were compared with their component tests by paired DeLong tests. Principal findings Ferritin showed a rise-peak-fall trajectory across hospital days, peaking on Day 3 (mean 955 ± 177 ng/ml; Friedman p < 10 −16 ); by day of illness it rose from a median of 700 ng/ml (illness days ≤3) to 950 ng/ml (days 6–7) and then plateaued. FPR Day 1 separated the severity groups with AUC 0.704 (95% CI 0.579–0.830); severe patients showed five-fold higher median FPR than non-severe patients (39.0 vs 7.5; p = 0.001). Against shock/DSS, FPR Day 1 had AUC 0.801 (95% CI 0.688–0.898), no higher than platelet count alone (AUC 0.784; DeLong p = 0.41). FLR Day 1 discriminated severe hepatitis with AUC 0.995 (95% CI 0.988–1.000), no higher than ALT alone (AUC 1.000; DeLong p = 0.23), the variable that defines this outcome. Against non-circular outcomes, Ferritin Day 1 discriminated shock/DSS with AUC 0.789 and severe thrombocytopenia with AUC 0.727. The ferritin-platelet inverse correlation was demographic-independent (partial Spearman rho=−0.392; p < 0.001). Ferritin offered no incremental benefit over platelet count alone (NRI = 0.143; IDI = 0.000). Conclusions/significance Serum ferritin rose from admission to hospital Day 3 and was higher in patients with shock and severe thrombocytopenia. The Ferritin-to-Platelet Ratio and the Ferritin/ALT Ratio are low-cost, but neither discriminated better than the routine test it contains (platelet count or ALT). Because platelet count and transaminases entered the ratios as the lowest and highest values of the admission, and outcomes were recorded over the whole stay, both ratios are markers of disease severity rather than predictors of later shock or severe hepatitis. Prospective multi-centre studies with laboratory values and outcomes timed from admission are needed to test any predictive role.
Source: PLoS neglected tropical diseases
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,670
OpenAlex ID: W7169027260