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Characterization of circulating thrombin in patients with septic shock: a prospective observational study

  • Tobias BecherEmail author
  • Jens Müller
  • Ibrahim Akin
  • Stefan Baumann
  • Ksenija Stach
  • Martin Borggrefe
  • Bernd Pötzsch
  • Dirk Loßnitzer
Article
  • 28 Downloads

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.

Keywords

Hemostasis Mortality Sepsis Shock, septic Thrombin 

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

Notes

Acknowledgements

The authors thank the Klaus Tschira Charitable Foundation for its kind support. The authors further thank Simone Gasper for expert technical assistance.

Authors’ contributions

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

Funding

This study was funded by the Klaus Tschira Charitable Foundation (Grant No. 00.271.2015).

Compliance with ethical standards

Conflict of interest

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.

Ethical approval

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.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.First Department of Medicine, Faculty of Medicine Mannheim, University Medical Center Mannheim (UMM)University of HeidelbergMannheimGermany
  2. 2.Institute for Experimental Haematology and Transfusion Medicine, University of Bonn Medical Center (UKB)BonnGermany

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