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

Area of Science:

• Hematology
• Infectious Diseases
• Clinical Medicine

Background:

• Thrombocytopenia is a common clinical feature of dengue infection.
• The mechanisms driving thrombocytopenia in dengue are not fully understood.
• Platelet indices offer a potential avenue for mechanistic classification and risk assessment.

Purpose of the Study:

• To categorize dengue-associated thrombocytopenia phenotypes using platelet indices.
• To assess the association between these phenotypes and bleeding risk.
• To evaluate the diagnostic performance of platelet indices for predicting bleeding and develop a Dengue Bleeding Risk Score (DBRS).

Main Methods:

• A case-control study involving 334 dengue patients and 101 controls.
• Analysis of various platelet indices (PLT, PCT, IPF, MPC, MPV, PDW, PLCR, PLCC) and coagulation parameters.
• Classification of thrombocytopenia into four phenotypes (hyperdestructive, inadequate response, hypoproductive, lazy-suppressed) based on PLT and IPF; logistic regression and ROC analyses for bleeding risk.

Main Results:

• Thrombocytopenia observed in 82.9% of dengue cases, with 'inadequate response' being most frequent (55.7%).
• A shift towards the 'hyperdestructive' phenotype correlated with increased disease severity (p < 0.001).
• Severe dengue was the strongest predictor of bleeding (adjusted OR 41.83), while IPF and MPC showed moderate bleeding prediction (AUC ~0.72).

Conclusions:

• Dengue thrombocytopenia presents heterogeneous, mechanism-based phenotypes.
• Bleeding risk is predominantly driven by overall disease severity, not solely by the thrombocytopenia phenotype.
• Integrating platelet indices into models like the DBRS may enhance risk stratification beyond platelet count alone, requiring further validation.