Division of Acute and Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Hokkaido University Faculty of Medicine, Sapporo, Japan.
Emergency and Trauma Center, Kameda Medical Center, Kamogawa, Japan.
Front Immunol. 2022 Dec 9;13:1026163. doi: 10.3389/fimmu.2022.1026163. eCollection 2022.
Trauma 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.
This 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).
Patients 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.
Decreased antithrombin activity in trauma-induced coagulopathy is associated with poor outcomes through worsening of DIC.
创伤会激活先天免疫系统，调节止血功能，最大程度地减少生理反应造成的损害，包括凝血的激活。严重创伤会使生理反应不堪重负，并引发全身炎症反应综合征，导致弥散性血管内凝血（DIC）的发生，其特征是炎症性凝血纤溶反应失调。抗凝血酶等抗凝机制受损是 DIC 的病理学基础，而抗凝血酶的动态变化及其与创伤性凝血病结局的关系尚未完全阐明。本研究旨在探讨抗凝血酶活性与严重创伤患者 DIC 发病和结局的关系。
本研究是一项多中心前瞻性研究的回顾性亚分析，纳入创伤严重程度评分≥16 的患者。我们将抗凝血酶活性降低的创伤患者（入院时抗凝血酶＜80%，n=75）与抗凝血酶活性正常的患者（抗凝血酶≥80%，n=200）进行比较。评估了凝血和纤溶的整体标志物、凝血酶生成的分子标志物（可溶性纤维蛋白[SF]）以及抗凝标志物（抗凝血酶），以确认抗凝血酶与 DIC 发生和结局的关系，包括院内死亡率和多器官功能障碍综合征（MODS）。
抗凝血酶活性降低的患者休克、输血需求和院内死亡率更高。与正常 AT 组相比，低 AT 组 DIC 评分更高，器官功能障碍更严重。入院时的抗凝血酶活性是创伤患者发生 DIC 的独立预测因子，SF 水平随抗凝血酶值降低而升高（抗凝血酶活性＞85%）。入院 3 小时的抗凝血酶活性对院内死亡率具有良好的预测性能，且抗凝血酶和 DIC 的交叉乘积项的多变量 Cox 比例风险回归模型显示，DIC 患者的院内死亡率随抗凝血酶活性降低而增加。多变量逻辑回归模型显示，DIC 患者发生 MODS 的几率随抗凝血酶值降低而增加。
创伤性凝血病中抗凝血酶活性降低与 DIC 恶化导致的不良结局相关。
