Association of antithrombin with development of trauma-induced disseminated intravascular coagulation and outcomes

Abstract

IntroductionTrauma activates the innate immune system to modulate hemostasis and minimize the damage caused by physiological bodily responses, including the activation of coagulation. Sufficiently severe trauma overwhelms physiological responses and elicits the systemic inflammatory response syndrome, which leads to the onset of disseminated intravascular coagulation (DIC), characterized by dysregulated inflammatory coagulofibrinolytic responses. Impaired anticoagulant mechanisms, including antithrombin, constitutes the pathology of DIC, while the dynamics of antithrombin and relevance to outcomes in trauma-induced coagulopathy have not been fully elucidated. This study investigated the associations of antithrombin activity with DIC onset and outcomes in severely injured patients.MethodsThis retrospective sub-analysis of a multicenter, prospective study included patients with an injury severity score ≥16. We characterized trauma patients with low antithrombin activity (antithrombin <80% on hospital arrival, n = 75) in comparison with those who had normal antithrombin activity (antithrombin ≥80%, n = 200). Global markers of coagulation and fibrinolysis, molecular biomarkers for thrombin generation (soluble fibrin [SF]), and markers of anticoagulation (antithrombin) were evaluated to confirm the associations of antithrombin with DIC development and outcomes, including in-hospital mortality and the multiple organ dysfunction syndrome (MODS).ResultsPatients with low antithrombin activity had higher prevalence of shock, transfusion requirements, and in-hospital mortality. Higher DIC scores and more severe organ dysfunction were observed in the low AT group compared to that in the normal AT group. Antithrombin activity on arrival at the hospital was an independent predictor of the development of DIC in trauma patients, and levels of SF increased with lower antithrombin values (antithrombin activity > 85%). Antithrombin activity at 3 h showed good predictive performance for in-hospital mortality, and a multivariable Cox proportional-hazard regression model with a cross-product term between the antithrombin and DIC showed that the in-hospital mortality in patients with DIC increased with decreased antithrombin activity. A multivariable logistic regression model showed that the odds for the development of MODS in patients with DIC increased with lower antithrombin values.ConclusionDecreased antithrombin activity in trauma-induced coagulopathy is associated with poor outcomes through worsening of DIC.

Early coagulation changes and survival outcomes, a multi-perspective retrospective analysis post severe burn

“…In summary, following burn injuries, genetic variation perspectives indicate a somewhat heightened activation of negative regulatory mechanisms. This aligns with ndings from previous studies focusing on early trauma 24 ; however, further examination is required within the context of burn patients. Given the dynamic nature of burn injuries, the insights we have presented may necessitate additional validation through rigorous animal or clinical trials.…”

Identification of early coagulation changes associated with survival outcomes post severe burns from multiple perspectives

“…In summary, following burn injuries, genetic variation perspectives indicate a somewhat heightened activation of negative regulatory mechanisms. This aligns with findings from previous studies focusing on early trauma 24 ; however, further examination is required within the context of burn patients. Given the dynamic nature of burn injuries, the insights we have presented may necessitate additional validation through rigorous animal or clinical trials.…”

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“…97 A recent clinical study has also indicated that the correction of antithrombin activity may contribute to improving the outcomes of trauma cases. 98 Importantly, this study suggested that it is necessary to consider the type of hemorrhage (simple type bleeding or oozing type bleeding), the type of coagulation changes (DIC or not), and when antithrombin should be administered (acute phase or subacute phase) to effectively identify target populations that benefit from anticoagulant therapies. 98 Definite DIC diagnosis and confirmation of the existence of systemic pathologic hyperfibrin(ogen)olysis appear to be the initial steps in the treatment of DIC with a fibrinolytic phenotype.…”