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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).)

Background: We conducted a prospective observational study for investigating the changes in the 13th member of a disintegrin-like and metalloprotease with thrombospondin type 1 motif (ADAMTS13) and its association with the coagulofibrinolytic response in adult trauma patients. Methods: In 39 trauma patients hospitalized for longer than 7 days, time-course changes in biomarkers of coagulofibrinolysis and systemic inflammation along with ADAMTS13 activity were examined. The patients were stratified into three groups based on ADAMTS13 activities on admission (day 0): normal group (≥70%), mildly decreased group (≥50 and < 70%) and moderately decreased group (< 50%). Results: Among 39 patients with a median Injury Severity Score (ISS) of 20, 11 patients developed disseminated intravascular coagulation (DIC) and 16 patients required transfusion. Six of 39 patients (15.4%) showed moderate decreased ADAMTS13 activity to < 50%, and 20 patients (51.3%) showed mild drops (≥50 and < 70%). These changes in ADAMTS13 activity on day 0 were significantly correlated with changes in IL-6 and other coagulofibrinolytic markers such as platelet counts, prothrombin time and fibrin/fibrinogen degradation product (FDP). Antithrombin activity (AT) and serum albumin (Alb) level showed significantly positive linear correlations with ADAMTS13 activity (AT: r = 0.513, p < 0.001; Alb: r = 0.647, p < 0.001). Simple logistic regression analyses showed that ADAMTS13 activity, if less than 50%, was significantly correlated with the development of DIC (OR 7.499, 95%CI 1.121–49.242, p = 0.038) and the need for transfusion of fresh frozen plasma (OR 9.000, 95%CI 1.327–61.025, p = 0.028). Conclusions: ADAMTS13 activity decreased even in the early phase of trauma, which was complicated by coagulopathy and systemic inflammation. Furthermore, the decrease in ADAMTS13 activity was correlated with DIC and plasma transfusion. [ABSTRACT FROM AUTHOR]

Background: We conducted a prospective observational study for investigating coagulofibrinolytic changes and mechanisms of antithrombin (AT) alternations in trauma. Methods: Trauma patients hospitalized for more than seven days were analyzed for coagulofibrinolytic biomarkers. The patients were stratified into two groups according to AT activity level on admission (day 0), comprising normal AT and low AT patients. Results: Thirty-nine patients (median Injury Severity Score 20) exhibited initial coagulatory activation and triphasic fibrinolytic changes. AT activity did not show a negative linear correlation with levels of thrombin-antithrombin complex (TAT), a marker of coagulation activity and AT consumption, but was strongly correlated with levels of albumin (Alb), an index of vascular permeability, on day 0 ( r = 0.702, p < 0.001). Furthermore, Alb was one of the independent predictors for AT on day 0. IL-6 on day 0 and thrombomodulin (TM) levels during the study period, reflecting systemic inflammation and endothelial cell injury, respectively, were significantly higher in the lower AT group ( n = 10) than in the normal group ( n = 29) (IL-6, p = 0.004; TM, p = 0.017). On days 2 and 4, TAT levels in the lower AT group were significantly higher than in the normal group. Conclusions: Trauma caused clear triphasic coagulofibrinolytic changes. Decreased AT in the later phase might lead to a prolonged hypercoagulation. AT reduction in the initial phase of trauma is strongly associated with extravascular leakage as suggested by the association of Alb depletion with IL-6 and TM elevation, but not with AT consumption. [ABSTRACT FROM AUTHOR]