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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., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: The research adhered to the principles of the Declaration of Helsinki and the Institutional Review Board of Ehime University Hospital approved this study (Approval number: 1902014). All patients or a legally authorized representative provided informed consent for the preservation and research use of blood components remaining from clinical tests., (© 2024. The Author(s).)

We analyzed the Nationwide Registry database on sepsis to examine the effects of an anticoagulation therapy, especially with rh-thrombomodulin (rh-TM) and/or antithrombin (AT) III agent, in septic disseminated intravascular coagulation (DIC) patients. In 3,193 patients enrolled after the exclusion, we investigated the association with in-hospital mortality using Cox proportional hazards models. DIC was diagnosed using the Japanese Association of Acute Medicine (JAAM) and the International Society of Thrombosis and Hemostasis (ISTH) criteria. To analyze the separate treatment effects of rh-TM and/or AT III, we excluded the data of 345 patients treated with all available anticoagulation treatments (rh-TM and/or AT III plus "other anticoagulants": protease inhibitors and heparin/heparinoids). The DIC criterion populations were as follows: JAAM DICs, n = 1,891 and ISTH DICs (overt DIC), n = 1,002. Septic DIC patients were divided into 3 groups: Group 1, no anticoagulation therapy for DIC; Group 2, received rh-TM and/or AT III; and Group 3, received only "other anticoagulants." In JAAM DIC patients, Group 2 did not show an independent association with a reduced risk of in-hospital mortality (hazard ratio [HR]: 0.86; 95% confidence interval [CI]: 0.73-1.01]) as compared with Group 1. However, in ISTH DIC patients, Group 2 showed an inverse association with the risk of in-hospital mortality (HR 0.74; 95% CI: 0.60-0.92) as compared with Group 1, but the same was not true for Group 3 (HR 0.73; 95% CI: 0.47-1.14). The present results support previous findings of the beneficial effects of anticoagulation therapies in septic DIC, also expands the importance of using rh-TM and/or AT agent for septic overt DIC.

Background: The purpose of this study was to evaluate the association between endotheliopathy represented by high levels of circulating syndecan-1 (SDC-1) and coagulofibrinolytic responses due to trauma, which can lead to disseminated intravascular coagulation (DIC). Methods: We retrospectively evaluated 48 eligible trauma patients immediately admitted to our hospital and assessed SDC-1 and coagulofibrinolytic parameters for 7 days after admission. We compared the longitudinal changes of coagulofibrinolytic parameters and SDC-1 levels between two groups (high and low SDC-1) according to median SDC-1 value on admission. Results: The median circulating SDC-1 level was 99.6 (61.1–214.3) ng/mL on admission, and levels remained high until 7 days after admission. Coagulofibrinolytic responses assessed by biomarkers immediately after trauma were correlated with SDC-1 elevation (thrombin–antithrombin complex, TAT: r = 0.352, p = 0.001; antithrombin, AT: r = −0.301, p < 0.001; plasmin-α2-plasmin inhibitor complex, PIC: r = 0.503, p = 0.035; tissue plasminogen activator, tPA: r = 0.630, p < 0.001). Sustained SDC-1 elevation was associated with intense and prolonged coagulation activation, impairment of anticoagulation, and fibrinolytic activation followed by inhibition of fibrinolysis, which are the primary responses associated with development of DIC in the acute phase of trauma. Elevation of circulating SDC-1 level was also associated with consumption coagulopathy and the need for transfusion, which revealed a significant association between high SDC-1 levels and the development of DIC after trauma (area under the curve, AUC = 0.845, cut-off value = 130.38 ng/mL, p = 0.001). Conclusions: High circulating levels of syndecan-1 were associated with intense and prolonged coagulation activation, impairment of anticoagulation, fibrinolytic activation, and consumption coagulopathy after trauma. Endotheliopathy represented by SDC-1 elevation was associated with trauma induced coagulopathy, which can lead to the development of DIC. [ABSTRACT FROM AUTHOR]