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Significance of plasma fibrinogen level and antithrombin activity in sepsis: A multicenter cohort study using a cubic spline model.
Thromb Res 2019; 181:17-23TR

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.

Authors+Show Affiliations

Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.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.Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.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.Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.Emergency and Trauma Center, Kameda Medical Center, Kamogawa, Japan.Division of Emergency and Critical Care Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.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.Department of Trauma and Critical Care Medicine, Kyorin University School of Medicine, Tokyo, Japan.Department of Emergency Medicine, Niizashiki Chuo General Hospital, Saitama, Japan.Trauma and Acute Critical Care Center, Medical Hospital, Tokyo Medical and Dental University, Tokyo, Japan.Division of Trauma and Surgical Critical Care, Osaka General Medical Center, Osaka, Japan.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31325905

Citation

Matsubara, Tsunehiro, et al. "Significance of Plasma Fibrinogen Level and Antithrombin Activity in Sepsis: a Multicenter Cohort Study Using a Cubic Spline Model." Thrombosis Research, vol. 181, 2019, pp. 17-23.
Matsubara T, Yamakawa K, Umemura Y, et al. Significance of plasma fibrinogen level and antithrombin activity in sepsis: A multicenter cohort study using a cubic spline model. Thromb Res. 2019;181:17-23.
Matsubara, T., Yamakawa, K., Umemura, Y., Gando, S., Ogura, H., Shiraishi, A., ... Fujimi, S. (2019). Significance of plasma fibrinogen level and antithrombin activity in sepsis: A multicenter cohort study using a cubic spline model. Thrombosis Research, 181, pp. 17-23. doi:10.1016/j.thromres.2019.07.002.
Matsubara T, et al. Significance of Plasma Fibrinogen Level and Antithrombin Activity in Sepsis: a Multicenter Cohort Study Using a Cubic Spline Model. Thromb Res. 2019;181:17-23. PubMed PMID: 31325905.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Significance of plasma fibrinogen level and antithrombin activity in sepsis: A multicenter cohort study using a cubic spline model. AU - Matsubara,Tsunehiro, AU - Yamakawa,Kazuma, AU - Umemura,Yutaka, AU - Gando,Satoshi, AU - Ogura,Hiroshi, AU - Shiraishi,Atsushi, AU - Kushimoto,Shigeki, AU - Abe,Toshikazu, AU - Tarui,Takehiko, AU - Hagiwara,Akiyoshi, AU - Otomo,Yasuhiro, AU - Fujimi,Satoshi, AU - ,, Y1 - 2019/07/02/ PY - 2019/03/05/received PY - 2019/06/04/revised PY - 2019/07/01/accepted PY - 2019/7/22/pubmed PY - 2019/7/22/medline PY - 2019/7/21/entrez KW - Critically ill KW - Disseminated intravascular coagulation KW - Marker KW - Septic shock SP - 17 EP - 23 JF - Thrombosis research JO - Thromb. Res. VL - 181 N2 - 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. SN - 1879-2472 UR - https://www.unboundmedicine.com/medline/citation/31325905/Significance_of_plasma_fibrinogen_level_and_antithrombin_activity_in_sepsis:_A_multicenter_cohort_study_using_a_cubic_spline_model L2 - https://linkinghub.elsevier.com/retrieve/pii/S0049-3848(19)30285-3 DB - PRIME DP - Unbound Medicine ER -