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Acute fibrinolysis shutdown occurs early in septic shock and is associated with increased morbidity and mortality: results of an observational pilot study

Schmitt, Felix Carl Fabian ; Manolov, Vasil ; Morgenstern, Jakob ; Fleming, Thomas ; Heitmeier, Stefan ; Uhle, Florian ; Al-Saeedi, Mohammed ; Hackert, Thilo ; Bruckner, Thomas ; Schöchl, Herbert ; Weigand, Markus Alexander ; Hofer, Stefan ; Brenner, Thorsten

In: Annals of intensive care, 9 (2019), Nr. 19. pp. 1-15. ISSN 2110-8520

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Download (2MB) | Lizenz: Creative Commons LizenzvertragAcute fibrinolysis shutdown occurs early in septic shock and is associated with increased morbidity and mortality: results of an observational pilot study by Schmitt, Felix Carl Fabian ; Manolov, Vasil ; Morgenstern, Jakob ; Fleming, Thomas ; Heitmeier, Stefan ; Uhle, Florian ; Al-Saeedi, Mohammed ; Hackert, Thilo ; Bruckner, Thomas ; Schöchl, Herbert ; Weigand, Markus Alexander ; Hofer, Stefan ; Brenner, Thorsten underlies the terms of Creative Commons Attribution 4.0

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Abstract

Background: Septic coagulopathy represents a very dynamic disease entity, tilting from initial hypercoagulability towards a subsequent hypocoagulable disease state, entitled overt disseminated intravascular coagulation. Acute fibrinolysis shutdown has recently been described to be a crucial component of initial hypercoagulability in critically ill patients, although the underlying pathomechanisms, the specific temporal kinetics and its outcome relevance in patients with sepsis remain to be determined.

Methods: In total, 90 patients (30 with septic shock, 30 surgical controls and 30 healthy volunteers) were enrolled. Blood samples were collected at sepsis onset or prior and immediately after the surgical procedure as well as 3 h, 6 h, 12 h, 24 h, 48 h and 7 d later, whereas blood samples from healthy volunteers were collected once. Besides viscoelastic and aggregometric point-of-care testing (POCT), enzyme-linked immunosorbent and thrombin generation assays and liquid chromatography–mass spectrometry-based measurements were performed.

Results: As assessed by viscoelastic POCT, fibrinolysis shutdown occurred early in sepsis. Significant increases in tissue plasminogen activator had no effect on thromboelastometrical lysis indices (LIs). Contrariwise, plasminogen activator inhibitor-1 was already significantly increased at sepsis onset, which was paralleled by significantly increased LIs in patients suffering from septic shock in comparison with both control groups. This effect persisted throughout the 7-day observation period and was most pronounced in severely ill as well as non-surviving septic patients. Thromboelastometrical LI, therefore, proved to be suitable for early diagnosis [e.g. LI 45 min: area under the curve (AUC) up to 0.933] as well as prognosis (e.g. LI 60 min: AUC up to 1.000) of septic shock.

Conclusions: Early inhibition of plasminogen activation leads to acute fibrinolysis shutdown with improved clot stability and is associated with increased morbidity and mortality in septic patients. Trial registration This study was approved by the local ethics committee (Ethics Committee of the Medical Faculty of Heidelberg; Trial-Code No. S247-2014/German Clinical Trials Register (DRKS)-ID: DRKS00008090; retrospectively registered: 07.05.2015). All study patients or their legal representatives signed written informed consent.

Item Type: Article
Journal or Publication Title: Annals of intensive care
Volume: 9
Number: 19
Publisher: Springer
Place of Publication: Heidelberg
Date Deposited: 20 Mar 2019 15:09
Date: 2019
ISSN: 2110-8520
Page Range: pp. 1-15
Faculties / Institutes: Medizinische Fakultät Heidelberg > Medizinische Universitäts-Klinik und Poliklinik
Medizinische Fakultät Heidelberg > Universitätsklinik für Anaesthesiologie
Medizinische Fakultät Heidelberg > Institut für Medizinische Biometrie und Informatik
Subjects: 610 Medical sciences Medicine
Uncontrolled Keywords: Fibrinolysis shutdown, Rotational thromboelastometry, Point-of-care testing, Thrombin–antithrombin, Plasminogen activator inhibitor 1, Tissue plasminogen activator, Thrombin generation assay
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