Longitudinal Trajectories of Platelet Indices Across Dengue Severity in Children: A Linear Mixed-Model Analysis

Background Dengue has a high disease burden, and some affected children progress to severe dengue (SD), making early identification of deterioration a clinical priority. Automated platelet indices such as mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) are generated at no additional cost by routine hematology analyzers. However, they are usually interpreted as static measurements and cannot distinguish peripheral platelet destruction from impaired bone marrow production. Linear mixed modeling (LMM) is well suited to correlated repeated measurements but has rarely been applied to platelet-index kinetics in pediatric dengue, particularly to distinguish dengue with warning signs (DWS) from SD. The objective of this study was to compare the longitudinal trajectories of eight automated platelet indices across dengue severity groups in hospitalized children using LMM and to assess whether platelet-index trajectories provide additional information beyond platelet count alone. Methods This prospective observational cohort included 130 children with dengue: 14 with dengue fever (DF), 80 with DWS, and 36 with SD, enrolled at a tertiary referral center. Platelet count, PCT, MPV, PDW, mean platelet component (MPC), mean platelet mass (MPM), large platelet percentage, and the composite platelet index (CPLI) were measured on study days 1, 3, 5, and 7. Study day 1 was the enrolment/admission day, which occurred within five days of fever onset. Separate LMMs were fitted for each index with fixed effects of severity group, illness day, age, sex, and a severity × day interaction, and a patient-level random intercept. Results Five indices were associated with dengue severity. Platelet count (day × severity interaction, p < 0.001), PCT (p < 0.001), large platelet percentage (p = 0.035), and CPLI (p < 0.001) showed significant severity-dependent trajectories. MPC was significantly associated with severity overall (p = 0.004), with a borderline day × severity interaction (p = 0.066). MPC showed progressive decline in SD from 26.1 g/dL (day 1) to 24.4 g/dL (day 5), signalling sustained platelet activation while remaining stable in DF. By day 3, CPLI was the only index with non-overlapping 95% confidence intervals between SD (1.46-3.74) and DWS (3.78-5.27). Large platelet percentage increased from 1.63% to 2.29% in DWS between study days 1 and 3 (absolute increase, 0.66 percentage points), compared with an increase from 1.18% to 1.28% in SD (absolute increase, 0.10 percentage points). This pattern is consistent with preserved compensatory thrombopoiesis in DWS and impaired compensation in SD. An exploratory day-1 profile of low platelet count, low CPLI, and a low large platelet percentage was observed in SD. MPV, PDW, and MPM did not discriminate by severity. Conclusions Platelet count, PCT, large platelet percentage, and CPLI showed severity-associated longitudinal trajectories in hospitalized children with dengue. The SD pattern is consistent with concurrent platelet consumption and impaired compensatory thrombopoiesis. These findings require multicenter validation, analyzer standardization, and formal prognostic evaluation before clinical application.