Abstract
Septic shock is characterized by a dysregulated response to infection, hypotension and activation of the coagulation system. Markers of coagulation activation are commonly used to diagnose and monitor ensuing coagulopathies. In this study, we sought to determine levels of circulating thrombin in patients with septic shock. To characterize levels of circulating, active thrombin in patients with septic shock. 48 patients with septic shock were included in this prospective, observational study. Blood samples were obtained on admission, day 1, day 3 and day 6. Levels of active thrombin were measured using a standardized, clinically applicable oligonucleotide (aptamer)-based enzyme-capture assay (OECA). Thrombin levels were correlated with established indirect thrombin parameters, conventional coagulation tests, laboratory parameters, patient characteristics and outcome. Elevated levels of thrombin were detected in 27 patients (56.3%) during the course of the study. Thrombin levels were positively correlated with thrombin-antithrombin complexes (r = 0.30, p < 0.05) and negatively associated with FVII levels (r = − 0.28, p < 0.05). Thrombin levels on admission did not predict 30-day mortality (OR 0.82, 95% CI 0.23–2.92, p = 0.77). Circulating levels of active thrombin can be measured in a subset of patients with septic shock. Although thrombin levels are correlated with established markers of coagulation, they do not provide additional prognostic information.
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Data availability
The datasets analysed are available from the corresponding author on reasonable request.
Abbreviations
- ANOVA:
-
Analysis of variance
- APACHE II:
-
Acute physiology and chronic health evaluation II
- APC:
-
Activated protein C
- aPTT:
-
Activated partial thromboplastin time
- ATIII:
-
Antithrombin
- CRP:
-
C-reactive protein
- DD:
-
D-dimer
- DIC:
-
Disseminated intravascular coagulation
- F1 + F2:
-
Prothrombin activation fragment F1 + 2
- FVII:
-
Coagulation factor VII
- ICU:
-
Intensive care unit
- INR:
-
International normalized ratio
- IQR:
-
Interquartile range
- LLOQ:
-
Lower limit of quantification
- NOAC:
-
New oral anticoagulant
- OECA:
-
Oligonucleotide (aptamer)-based enzyme-capture assay
- PC:
-
Protein C
- PCT:
-
Procalcitonin
- SAPS:
-
Simplified Acute Physiology Score
- SC:
-
Septic coagulopathy
- SD:
-
Standard deviation
- TF:
-
Tissue factor
- TAT:
-
Thrombin-antithrombin complexes
- VKA:
-
Vitamin K antagonist
- WBC:
-
White blood cell count
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Acknowledgements
The authors thank the Klaus Tschira Charitable Foundation for its kind support. The authors further thank Simone Gasper for expert technical assistance.
Funding
This study was funded by the Klaus Tschira Charitable Foundation (Grant No. 00.271.2015).
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TB, SB and DL designed the study and drafted the manuscript. JM and KS analysed and interpreted the data. IA was a major contributor in writing the manuscript. BP, DL, JM and MB revised the manuscript critically for important intellectual content. All authors read and approved the final manuscript
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Martin Borggrefe declares financial relations, including speaker honoraria and research grants, with Boston Scientific, Medtronic, Impulse Dynamics, St. Jude Medical, CVRx, Biotronic, Pfizer, Bayer and Böhringer-Ingelheim. All other authors declare that they have no conflict of interest.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee (University of Heidelberg, Germany; reference number 2015-526N-MA) and with the 1964 Helsinki declaration and its later amendments.
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Informed consent was obtained from all individual participants included in the study.
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Becher, T., Müller, J., Akin, I. et al. Characterization of circulating thrombin in patients with septic shock: a prospective observational study. J Thromb Thrombolysis 50, 90–97 (2020). https://doi.org/10.1007/s11239-019-01992-w
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DOI: https://doi.org/10.1007/s11239-019-01992-w