Abstract
We carried out a retrospective observational investigation to explore the association of endotheliopathy with coagulofibrinolytic reactions and the progression of disseminated intravascular coagulation (DIC) in adult trauma patients. We measured syndecan-1 (SDC-1), an indicator of endotheliopathy, and biomarkers of coagulofibrinolysis in 100 trauma patients immediately transferred to Ehime University Hospital. We evaluated the correlations between the coagulofibrinolytic parameters and SDC-1. We also investigated the association between SDC-1 elevations and the development of DIC, and determined the discriminators of DIC development. The median SDC-1 concentration was 82.7 (43.5-178.1) ng/mL. DIC developed in 16 patients (16.0%), and SDC-1 concentrations were significantly higher in DIC patients than in non-DIC patients (218.8 [134.5-798.2] ng/mL vs. 67.2 [39.6-114.5] ng/mL, p < 0.001). Receiver operating characteristic curve analysis revealed that the circulating SDC-1 level effectively predicted the progression of DIC, with an area under the curve of 0.862 (95% confidence interval [CI], 0.789-0.936). The optimal cut-off value was determined to be 92.5 ng/mL, yielding a sensitivity of 100.0% and a specificity of 67.8% (p < 0.001). A simple logistic regression analysis showed that a circulating SDC-1 concentration of > 92.5 ng/mL was significantly correlated with DIC progression (odds ratio [OR], 31.67; 95%CI: 3.97-252.31, p = 0.001). Many coagulofibrinolytic parameters were significantly correlated with SDC-1. Estimating the discriminators of DIC development by the least absolute shrinkage and selection operator (LASSO) and elastic-net regression analysis identified markers of coagulofibrinolytic activation, such as thrombin-antithrombin complex (TAT) and tissue plasminogen activator (tPA). A multivariate logistic regression model using TAT, tPA, and SDC-1 demonstrated that TAT and tPA, but not SDC-1, were independent factors predicting the development of DIC (TAT per 10 µg/L: OR, 1.14, 95%CI: 1.05-1.24, p = 0.003; tPA per 100pg/mL: OR, 1.03, 95%CI: 1.01-1.05, p = 0.003; SDC-1 per 10ng/mL: OR, 1.00, 95%CI: 0.99-1.01, p = 0.973). Mediation analysis showed that SDC-1 elevation was predominantly associated with the development of DIC indirectly through the increase in TAT (proportion mediated = 96.1%, p < 0.001), while there was no significant indirect effect of SDC-1 elevation on the role of TAT elevation in DIC development was observed (p = 0.340). The primary pathogenesis of DIC in the acute phase of trauma is likely driven by coagulofibrinolytic activation. Endotheliopathy, as reflected by elevated circulating levels of SDC-1, is strongly associated with coagulofibrinolytic responses. Although endotheliopathy may contribute to the early development of DIC through coagulation activation, its role appears to be limited.