AIMS: This study explores the changes in thrombosis-related indicators in patients with severe fever with thrombocytopenia syndrome (SFTS), providing a basis for early diagnosis, treatment, and disease monitoring. METHODS: The patients were divided into mild and severe groups, as well as survivor and non-survivor groups. Forty-five healthy individuals were included as a control group. We compared the activity of thrombosis-related markers in these groups. The risk of developing severe disease and death in patients was predicted using receiver operating characteristic (ROC) curve analysis. We also examined the correlation between thrombomodulin (TM) and clinical lab parameters in the plasma of SFTS patients. RESULTS: Comparison among the mild, severe, and healthy control groups revealed that the levels of TM, thrombin-antithrombin complex (TAT), plasmin-antiplasmin complex (PIC), and tissue plasminogen activator-plasminogen activator inhibitor complex (t-PAIC) were significantly higher in severe patients than in the healthy control group (P <
0.05). Comparison between the survivor and non-survivor groups showed that the levels of TM, TAT, and t-PAIC in the non-survivor group were higher than those in the survivor group, and the differences were statistically significant (P <
0.05). ROC analysis showed that TM had a higher predictive ability for the risk of severe disease (area under the ROC curve [AUROC] = 0.931). Additionally, TM (AUROC = 0.817) and t-PAIC (AUROC = 0.824) had higher predictive abilities for the risk of death. TM was positively correlated with thrombin time (TT), d-dimer (D-D), creatinine (CREA), total bile acid (TBA), and c-reactive protein (CRP), and negatively correlated with cholesterol (CHOL), high density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and platelet (PLT). CONCLUSION: Monitoring thrombosis-related indicators in SFTS patients is crucial for assessing disease severity. Early symptomatic treatment can significantly reduce the rate of severe cases and prevent patient mortality.