TY  - JOUR
IS  - 19
AV  - public
PB  - Springer
ID  - heidok26020
VL  - 9
EP  - 15
CY  - Heidelberg
JF  - Annals of intensive care
N2  - 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.
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/26020/
SP  - 1
A1  - Schmitt, Felix Carl Fabian
A1  - Manolov, Vasil
A1  - Morgenstern, Jakob
A1  - Fleming, Thomas
A1  - Heitmeier, Stefan
A1  - Uhle, Florian
A1  - Al-Saeedi, Mohammed
A1  - Hackert, Thilo
A1  - Bruckner, Thomas
A1  - Schöchl, Herbert
A1  - Weigand, Markus Alexander
A1  - Hofer, Stefan
A1  - Brenner, Thorsten
KW  - Fibrinolysis shutdown
KW  -  Rotational thromboelastometry
KW  -  Point-of-care testing
KW  -  Thrombin?antithrombin
KW  -  Plasminogen activator inhibitor 1
KW  -  Tissue plasminogen activator
KW  -  Thrombin generation assay
SN  - 2110-8520
TI  - Acute fibrinolysis shutdown occurs early in septic shock and is associated with increased morbidity and mortality: results of an observational pilot study
Y1  - 2019///
ER  -