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Published on: May 5, 2023
Importance of endothelial dysfunction biomarkers in patients with Crimean-Congo hemorrhagic fever
Mustafa Arslan1, Gürdal Yilmaz2, Ahmet Mentese3
1Department of Infectious Diseases and Clinical Microbiology, Amasya University Sabuncuoglu Serefeddin Training and Research Hospital, Amasya, Turkey.
Insights
Crimean-Congo hemorrhagic fever (CCHF) involves endothelial dysfunction. Markers like asymmetrical dimethyl arginine (ADMA) and thrombomodulin (TM) indicate injury severity and may predict hemorrhage in CCHF patients.
Area of Science:
- Vascular Biology and Pathology
- Infectious Diseases Epidemiology
- Biomarker Discovery
Background:
- The exact pathogenesis of Crimean-Congo hemorrhagic fever (CCHF) and its hemorrhagic complications remain unclear.
- Endothelial cells are recognized as critical players in CCHF pathogenesis and the development of hemorrhage.
Purpose of the Study:
- To investigate serum endothelial dysfunction markers in CCHF patients.
- To assess the association between these markers and the occurrence of hemorrhage in CCHF.
Main Methods:
- Serum levels of endothelial dysfunction markers, including asymmetrical dimethyl arginine (ADMA), endothelin 1 (ET-1), thrombomodulin (TM), von Willebrand factor (vWf), and intercellular adhesion molecule (ICAM-1), were measured in 73 CCHF patients.
- Patients were compared to healthy controls, and hemorrhagic and non-hemorrhagic groups were analyzed.
- Statistical analyses were performed to determine significant differences and associations.
Main Results:
- Significant differences in ADMA, ET-1, TM, vWf, and ICAM-1 levels were observed between CCHF patients and healthy controls upon hospital admission.
- Thrombomodulin (TM) and von Willebrand factor (vWf) levels were significantly different between hemorrhagic and non-hemorrhagic CCHF patient groups.
- Serum ADMA and TM levels increased from day 1 to day 5 in both hemorrhagic and non-hemorrhagic CCHF groups, correlating with endothelial injury severity.
Conclusions:
- Endothelial dysfunction markers in CCHF reflect the extent of endothelial damage.
- Asymmetrical dimethyl arginine (ADMA) and thrombomodulin (TM) may serve as early indicators of hemorrhage risk in CCHF.
- Elevated ADMA and compromised coagulation due to increased soluble TM contribute to endothelial injury and hemorrhage in CCHF.
Abstract:
The pathogenesis of the Crimean-Congo hemorrhagic fever (CCHF) and the cause of the hemorrhage are not yet fully understood. However, the endothelium plays a key role in the pathogenesis. The purpose of this study was to investigate endothelial dysfunction markers (asymmetrical dimethyl arginine [ADMA], endothelin 1[ET-1], thrombomodulin [TM], von Willebrand factor [vWf], and intercellular adhesion molecule [ICAM-1]) in serum in patients with CCHF and their associations with hemorrhage. Seventy-three patients with CCHF were included in the study. All patients' endothelial dysfunction markers were studied using routine biochemical and hematological tests. The data obtained were then subjected to statistical analysis. Statistically significant differences were determined between the patients and healthy control groups at time of presentation to hospital in terms of ADMA (P < 0.001), ET-1 (P < 0.001), TM (P = 0.039), vWf (P < 0.001), and ICAM-1 (P < 0.001) levels. Only the differences in TM and vWf were significant between the hemorrhagic and non-hemorrhagic groups (P < 0.05). Both serum ADMA and TM levels were significantly higher in the hemorrhage and non-hemorrhage CCHF groups on the 5th day compared to the 1st day (P < 0.05). Levels of endothelial dysfunction markers in CCHF vary in proportion to the damage occurring in the endothelium. ADMA and TM levels were lower in periods with mild endothelial injury. They were increased in line with severity endothelial injury. They may be an early marker in showing hemorrhage. Elevation in ADMA levels and low nitric oxide levels lead to endothelial injury and hemorrhage. Soluble TM that entered the circulation in line with the increased endothelial injury in hemorrhagic patients has been compromised the coagulation cascade.
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