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Elevated soluble thrombomodulin in the febrile stage related to patients at risk for dengue shock syndrome
Punnee Butthep1, Sirichan Chunhakan, Kanchana Tangnararatchakit
1Department of Pathology, Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Bangkok, Thailand. rapbt@mahidol.ac.th
Insights
Soluble thrombomodulin (sTM) may predict dengue shock syndrome (DSS) in children. Elevated sTM levels were found in patients with severe dengue hemorrhagic fever (DHF) and DSS, indicating potential as an early diagnostic marker.
Area of Science:
- Infectious Diseases
- Hematology
- Vascular Biology
Background:
- Children with dengue hemorrhagic fever (DHF) are at risk of developing dengue shock syndrome (DSS).
- Currently, no reliable early markers exist to predict DSS development in DHF patients.
Purpose of the Study:
- To identify early predictors of dengue shock syndrome (DSS) by investigating markers of vascular endothelial cell injury and dysfunction.
- To assess the potential of soluble thrombomodulin (sTM) as an early diagnostic marker for DSS.
Main Methods:
- Blood samples were collected daily from 111 patients with dengue fever, DHF, or other febrile illness (OFI).
- Samples were analyzed using enzyme-linked immunosorbent assay (ELISA) to measure soluble thrombomodulin (sTM) and other adhesion molecules.
- Patients were categorized based on disease severity (dengue fever, DHF grades I-IV, OFI) and sample timing relative to defervescence (day 0).
Main Results:
- Elevated soluble thrombomodulin (sTM) levels were observed in dengue-infected patients compared to OFI.
- Patients with severe DHF (grades III-IV) and DSS exhibited significantly higher sTM concentrations from day -3 to day +2 relative to defervescence.
- Increased circulating endothelial cells and adhesion molecules (sVCAM-1, sICAM-1, sE-selectin) were also detected in DSS patients.
Conclusions:
- Blood soluble thrombomodulin (sTM) shows promise as an early predictor of DSS in dengue-infected patients during the febrile stage.
- Further large-scale prospective studies are warranted to validate sTM as a reliable early diagnostic marker for DSS.
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.
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