Elevated soluble thrombomodulin in the febrile stage related to patients at risk for dengue shock syndrome

Background: Children with dengue hemorrhagic fever (DHF) are at risk to develop dengue shock syndrome (DSS) for which neither marker has been demonstrated. Objective: The study was designed to investigate the markers of vascular endothelial cell injuries and dysfunction that might be used as early predictors of the subsequent manifestation of DSS. Methods: The blood samples from 111 patients with dengue fever, DHF and other febrile illness (OFI) were collected daily from the day of admission until discharge and at convalescent stage. The sample from the day of defervescence was defined as day 0, 1 day before defervescence was defined as day -1 and so on. Also, 1 day after defervescence was defined as day +1 and so on. Results: Increased soluble thrombomodulin (sTM) was demonstrated in dengue-infected patients via an enzyme-linked immunosorbent assay. Patients with DSS (DHF grades III and IV) had higher concentrations of sTM than those with dengue fever, DHF grade I, II and OFIs from day -3 until day +2. Increased circulating endothelial cells were detected from day 0 until day +2 in DSS patients as compared with other groups. In addition, increased soluble vascular cell adhesion molecule-1, soluble intercellular adhesion molecule-1 and soluble E-selectin were also found in dengue virus-infected patients as compared with OFIs. Conclusion: Blood sTM may be useful as an early predictor of DSS in dengue infected patients in the febrile stage. However, a further evaluation in a large prospective series is needed.