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

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.

Difference of coagulation features between severe pneumonia induced by SARS-CoV2 and non-SARS-CoV2

“…The dysfunction of endothelial cells induced by infection results in excess thrombin generation and fibrinolysis shutdown, which indicated a hypercoagulable state in patient with infection [9,10]. In addition, hypoxia existed in severe pneumonia can stimulate thrombosis through not only increasing blood viscosity, but also a hypoxia-inducible transcription factor-dependent signaling pathway [11].…”

Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy

“…The dysfunction of endothelial cells induced by infection results in excess thrombin generation and fibrinolysis shutdown, which indicated a hypercoagulable state in patient with infection, 12,13 such as COVID‐19. In addition, the hypoxia found in severe COVID‐19 can stimulate thrombosis through not only increasing blood viscosity, but also a hypoxia‐inducible transcription factor‐dependent signaling pathway 14 .…”

Diagnosis and management of sepsis‐induced coagulopathy and disseminated intravascular coagulation

“…One hallmark of sepsis‐associated DIC is excessive suppression of fibrinolysis caused by overproduction of plasminogen activator inhibitor‐1, with potential for associated prothrombotic effects . In contrast, such suppression is rarely seen in malignancy‐associated DIC .…”

“…One hallmark of sepsis-associated DIC is excessive suppression of fibrinolysis caused by overproduction of plasminogen activator inhibitor-1, 18,19 with potential for associated prothrombotic effects. 20,21 In contrast, such suppression is rarely seen in malignancy-associated DIC. 22 As a result, organ dysfunction often develops in sepsis-associated DIC due to reduced tissue perfusion, while systemic bleeding is a more common feature in (nonsepsis) fibrinolytic phenotype DIC.…”