Thrombelastography for the monitoring of lipopolysaccharide induced activation of coagulation

Kai Zacharowski; Christoph Sucker; Paula Zacharowski; Matthias Hartmann

doi:10.1160/TH05-06-0420

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2006; 95(03): 557-561
DOI: 10.1160/TH05-06-0420

New Technologies, Diagnostic Tools and Drugs

Schattauer GmbH

Thrombelastography for the monitoring of lipopolysaccharide induced activation of coagulation

Authors

Kai Zacharowski^*

¹Department of Anesthesiology, University Hospital Düsseldorf, Germany

²Molecular Cardioprotection and Inflammation Group, University Hospital Düsseldorf, Germany
Christoph Sucker^*

³Department of Haemostasis and Transfusion Medicine, University Hospital Düsseldorf, Germany
Paula Zacharowski

¹Department of Anesthesiology, University Hospital Düsseldorf, Germany

²Molecular Cardioprotection and Inflammation Group, University Hospital Düsseldorf, Germany
Matthias Hartmann

¹Department of Anesthesiology, University Hospital Düsseldorf, Germany

Abstract

Summary

During Gram-negative sepsis, lipopolysaccharide (LPS) activates toll-like receptor (TLR) 4 and induces complex responses of immune system and haemostasis. In the present study we investigated whether thrombelastography is suitable to monitor the LPS-induced activation of coagulation. Whole blood samples from healthy volunteers were incubated with LPS for various in-cubation periods (0–5 hrs), thereafter rotation thrombelastography was performed. Incubation of whole blood (≥ 3 h) with LPS markedly reduced clotting time; after 5 hrs the variable was reduced from 459 ± 39 sec to 80 ± 20 sec while the other thrombelastography variables (angle α, clot formation time, maximal clot formation) remained unaltered. EC⁵⁰ of the LPSeffect on whole blood clotting time was 18 µg/ml.In isolated leu kocytes, diluted in platelet poor plasma, far lower LPS-concentrations were effective: 10 ng/ml LPS reduced clotting time from 439 ± 68 sec to 200± 56 sec. Experiments with the protein synthesis inhibitor cycloheximide and active site-inhibited factor VIIa revealed that LPS exerts its effects via the synthesis of tissue factor.Addition of tissue factor to whole blood samples revealed that a concentration of 100 fmol/l can be detected using thrombelastography. In whole blood samples the tissue factor concentration induced by LPS amounted up to 12 pmol/l. In summary, thrombelastography proved to bea sensitive and reliable tool for the determination of LPS-induced tissue factor mediated activation of haemostasis in whole blood samples.

Keywords

Human whole blood - lipopolysaccharide - thrombelastography

Full Text

References

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