Tsunehiro Matsubara1, Kazuma Yamakawa2, Yutaka Umemura1, Satoshi Gando3, Hiroshi Ogura1, Atsushi Shiraishi4, Shigeki Kushimoto5, Toshikazu Abe6, Takehiko Tarui7, Akiyoshi Hagiwara8, Yasuhiro Otomo9, Satoshi Fujimi10. 1. Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, Japan. 2. Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, Japan; Division of Trauma and Surgical Critical Care, Osaka General Medical Center, Osaka, Japan. Electronic address: k.yamakawa0911@gmail.com. 3. Department of Anesthesiology and Critical Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan; Acute and Critical Care Center, Department of Acute and Critical Care Medicine, Sapporo Higashi Tokushukai Hospital, Sapporo, Japan. 4. Emergency and Trauma Center, Kameda Medical Center, Kamogawa, Japan. 5. Division of Emergency and Critical Care Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan. 6. Department of General Medicine, Juntendo University, Health Services Research and Development Center, University of Tsukuba, Tsukuba, Japan; Health Services Research and Development Center, University of Tsukuba, Tsukuba, Japan. 7. Department of Trauma and Critical Care Medicine, Kyorin University School of Medicine, Tokyo, Japan. 8. Department of Emergency Medicine, Niizashiki Chuo General Hospital, Saitama, Japan. 9. Trauma and Acute Critical Care Center, Medical Hospital, Tokyo Medical and Dental University, Tokyo, Japan. 10. Division of Trauma and Surgical Critical Care, Osaka General Medical Center, Osaka, Japan.
Abstract
INTRODUCTION: Sepsis leads to coagulopathy by the activation of inflammatory mediators and vascular endothelial cell injury. A number of biomarkers are used to evaluate coagulopathy on sepsis. Fibrinogen and antithrombin activity have been reported as biomarkers of coagulopathy; however, the utility of these two markers has not been well established. This study aimed to evaluate the detailed association between these two markers and clinical outcomes in sepsis patients. MATERIALS AND METHODS: This was a post hoc analysis of a multicenter, prospective cohort study conducted in 59 intensive care units throughout Japan from January 2016 to March 2017. We included 1103 adult patients with severe sepsis based on the Sepsis-2 criteria. The associations between the coagulation markers and in-hospital mortality were examined using linear and non-linear logistic regression analyses. We also evaluated the associations between the coagulation markers and disseminated intravascular coagulation (DIC) scores. The International Society on Thrombosis and Haemostasis overt DIC score was calculated after subtracting the fibrinogen component. RESULTS: The decreased levels of the fibrinogen and antithrombin activity were significantly associated with an increase in mortality (P = 0.011 and 0.002, respectively). In addition, cubic spline regression demonstrated that mortality sharply increased at a fibrinogen level of approximately <200 mg/dL and at an antithrombin activity of approximately <50%. Similarly, the decreased levels of the two markers non-linearly correlated with the elevation of DIC score. CONCLUSIONS: The fibrinogen level and antithrombin activity should be reconsidered as unique biomarkers for sepsis and sepsis-induced DIC.
INTRODUCTION:Sepsis leads to coagulopathy by the activation of inflammatory mediators and vascular endothelial cell injury. A number of biomarkers are used to evaluate coagulopathy on sepsis. Fibrinogen and antithrombin activity have been reported as biomarkers of coagulopathy; however, the utility of these two markers has not been well established. This study aimed to evaluate the detailed association between these two markers and clinical outcomes in sepsispatients. MATERIALS AND METHODS: This was a post hoc analysis of a multicenter, prospective cohort study conducted in 59 intensive care units throughout Japan from January 2016 to March 2017. We included 1103 adult patients with severe sepsis based on the Sepsis-2 criteria. The associations between the coagulation markers and in-hospital mortality were examined using linear and non-linear logistic regression analyses. We also evaluated the associations between the coagulation markers and disseminated intravascular coagulation (DIC) scores. The International Society on Thrombosis and Haemostasis overt DIC score was calculated after subtracting the fibrinogen component. RESULTS: The decreased levels of the fibrinogen and antithrombin activity were significantly associated with an increase in mortality (P = 0.011 and 0.002, respectively). In addition, cubic spline regression demonstrated that mortality sharply increased at a fibrinogen level of approximately <200 mg/dL and at an antithrombin activity of approximately <50%. Similarly, the decreased levels of the two markers non-linearly correlated with the elevation of DIC score. CONCLUSIONS: The fibrinogen level and antithrombin activity should be reconsidered as unique biomarkers for sepsis and sepsis-induced DIC.
Authors: Charalampos Pierrakos; Dimitrios Velissaris; Max Bisdorff; John C Marshall; Jean-Louis Vincent Journal: Crit Care Date: 2020-06-05 Impact factor: 9.097