Beyond Hemostasis: Platelet Biomarkers and Vascular-Immune Crosstalk in Dengue

Abstract

Dengue is an arboviral disease with major global public health impact. Its pathophysiology involves complex interactions between the virus and the host, including the immune response and the vascular endothelium. In this context, platelets play roles beyond hemostasis, acting as key immunomodulatory cells involved in inflammation and the regulation of vascular permeability. Therefore, this review summarizes and discusses the so called classic and non-classic platelet-related and endothelial biomarkers described in dengue virus infection. Classical biomarkers include P-selectin (CD62P), PF4/CXCL4, RANTES/CCL5, CD40L, IL-1β, VEGF, integrin αIIbβ3, CD63, and platelet extracellular vesicles, all supported by broad experimental and clinical evidence. Non-classical or emerging biomarkers include TLT-1, TREM-1/sTREM-1, angiopoietins (Ang-1/Ang-2), serotonin, ferritin, dengue virus envelope domain III (EIII), and soluble endothelial molecules such as IL-1RA, sCD163, SDC-1, sVCAM-1, IL-8, and IP-10. Alone or in combination, these markers can be used/explored as prognostic tools and/or as therapeutic targets. Finally, integrating multimarker panels encompassing hemostatic, inflammatory, and endothelial pathways may improve prognostic stratification. This approach could support targeted interventions and help reduce complications such as thrombocytopenia, plasma leakage, and dengue shock.