Decoding Thrombocytopenia in Dengue: Platelet Indices Define Mechanistic Phenotypes and Predict Bleeding Risk

Background: Thrombocytopenia is a characteristic of dengue infection; however, the underlying mechanisms of these phenotypes remain underexplored clinically. Platelet indices may serve as a swift and accessible method for mechanistic distinction and risk assessment. Objective: The objective of this study was to evaluate platelet indices for mechanistic categorization of thrombocytopenia phenotypes in dengue patients, assess their association with bleeding risk, determine their diagnostic performance for bleeding prediction, and develop a preliminary Dengue Bleeding Risk Score (DBRS) for risk stratification. Method: A case-control study included 334 dengue cases and 101 controls. We examined platelet count (PLT), plateletcrit (PCT), immature platelet fraction (IPF), mean platelet component (MPC), mean platelet volume (MPV), platelet distribution width (PDW), platelet large cell ratio (PLCR), platelet large cell count (PLCC), and coagulation parameters. Thrombocytopenia was classified into four phenotypes: hyperdestructive, inadequate response, hypoproductive, and lazy-suppressed, based on PLT and IPF. Platelet indices, coagulation parameters, and clinical outcomes were analyzed. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to evaluate bleeding risk. Results: Thrombocytopenia was present in 82.9% of patients, with inadequate response being the most common phenotype (55.7%). A significant shift toward the hyperdestructive phenotype was observed as disease severity increased (p < 0.001). Bleeding differed significantly across phenotypes, with the highest frequency in the hyperdestructive group (57.1%). In unadjusted analysis, this phenotype was strongly associated with bleeding (OR 13.25, 95% CI 4.11-42.71, p < 0.001); however, this association was not independent after adjustment for disease severity (OR 2.83, 95% CI 0.59-13.60, p = 0.194). Severe dengue remained the strongest predictor of bleeding (adjusted OR 41.83, 95% CI 14.41-121.46, p < 0.001). IPF and MPC demonstrated moderate performance in predicting bleeding (area under the curve (AUC) 0.723 and 0.718, respectively). Conclusion: Thrombocytopenia in dengue is a heterogeneous, mechanism-based condition characterized by diverse phenotypes; however, bleeding risk is primarily determined by disease severity rather than phenotype alone. The incorporation of platelet indices into a composite model, such as the DBRS, may provide a more comprehensive approach to risk stratification than platelet count alone, although further validation in independent cohorts is required.