Plasma thrombomodulin is a valuable biomarker to predict the severity of hemorrhagic fever with renal syndrome caused by the Hantaan virus

Han-Dong Zhao ¹ Yan Zhang ² Xiao-Hong Wang ¹ Hong-Bo Qian ¹ Tong-Bo Yu ¹ Peng Li ¹ Kang-Xiao Ma ^1* Hong-Li Liu ^3*

• ¹ Shaanxi Provincial Hospital of Infectious Disease, Xi'an, China
• ² Xi’an Hospital of Traditional Chinese Medicine, Xi’an, Shaanxi Province, China
• ³ Xi'an No.4 Hospital, Xi'an, China

Objectives: This study aimed to investigate the Thrombomodulin (TM) levels in patients who suffered hemorrhagic fever with renal syndrome (HFRS) of varying severities, and to evaluate the predictive properties of TM for the seriousness of HFRS, thereby providing a clue for the monitoring and management of this patients in the future.: Chemiluminescence was used to determine the concentrations of TM in 196 patients with HFRS and 49 healthy controls. Conventional testing techniques were used to test the basic clinical reference values for leukocytes, platelets (PLT), C-reactive protein (CRP), creatine (Cr), uric acid (UA), and urea, and the values for activated partial thromboplastin time, prothrombin time, and fibrinogen. The colloidal gold method was used to measure HFRS antibody levels in the patients. The correlation of TM with conventional parameters was assessed using Spearman correlation analysis, and ordinal logistic regression analysis was used to analyze the severity risk factors. The predictive potency of TM for HFRS patients' severity was evaluated by receiver operating characteristics (ROC) curve analysis. Results: The concentrations of TM increased with disease severity and peaked in the critical type patients. In addition, plasma levels of TM were proportionally correlated with the levels of leukocytes (r= 0.4218; p<0.01), creatine (r= 0.3797; p<0.01), urea (r= 0.3763; p<0.01), uric acid (r= 0.3624; p<0.01), and C-reactive protein (r= 0.2767; p<0.01). Conversely, there was an inverse correlation between TM, platelet counts (r= -0.4509; p<0.01), and fibrinogen levels (r= -0.2431; p<0.01). Furthermore, TM demonstrated significant predictive value for the severity of HFRS with an area under the ROC curve (AUC) of 0.872(95% CI: 0.822-0.921, P<0.001) Conclusions: TM levels are associated with HFRS severity, suggesting that TM detection might be beneficial for monitoring the status and effective management of HFRS patients.