Usefulness of plasminogen activator inhibitor-1 as a predictive marker of mortality in sepsis

Abstract

BackgroundSepsis is one of the most significant causes of mortality in intensive care units. It indicates crosstalk between inflammation and coagulation. In this study, we aimed to identify prognostic markers among sepsis biomarkers and coagulation/fibrinolysis markers.MethodsPatients with sepsis according to the Sepsis-3 criteria were enrolled from January 2013 to September 2015. Univariate and multivariate logistic regression analyses were performed to identify an independent predictive marker of 28-day mortality among sepsis biomarkers and coagulation/fibrinolysis markers on ICU admission. Receiver operating characteristic analysis was performed; the optimal cutoff value of 28-day mortality was calculated using the predictive marker. Patients were classified into two groups according to the cutoff level of the predictive marker. Patient characteristics were compared between the groups.ResultsA total of 186 patients were enrolled in this study; the 28-day mortality was 19.4% (36/186). PAI-1 was identified as the only independent predictive marker of 28-day mortality by univariate and multivariate logistic regression. The area under the curve was 0.72; the optimal cutoff level was 83 ng/ml (sensitivity, 75%; specificity, 61%). Patients were classified into a higher group (PAI-1 level ≥83 ng/ml; n = 85) and a lower group (PAI-1 level <83 ng/ml; n = 101). All disseminated intravascular coagulation (DIC) scores and Sequential Organ Failure Assessment score were significantly higher in the higher group than in the lower group.ConclusionsPAI-1 can predict prognosis in sepsis patients. PAI-1 reflects DIC with suppressed fibrinolysis and organ failure, with microthrombi leading to microcirculatory dysfunction.

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

“…TF expressed on various cells or released from injured cells initiates the physiologically most important TF (extrinsic) pathway, whereas PAI-1 is known to be a strong inhibitor of the fibrinolytic system. PAI-1-mediated fibrinolysis shutdown has already been described in a pig model of endotoxin-induced DIC [33] as well as in human sepsis [36]. We were able to support these findings within the presented investigation.…”

Clinical significance of measuring plasminogen activator inhibitor-1 in sepsis

“…Amongst the significant diagnostic markers for overt DIC, TAT and PAI-1 were the best predictors of 28-day mortality (AUROC, 0.77 and 0.81, respectively). Following similar reports, Hoshino et al [ 3 ] reported that the elevated levels of PAI-1 was associated with the poor outcome and the AUROC for 28-day mortality was 0.72, and the optimal cutoff level was 83 ng/mL. What were unique in their observations were firstly, only PAI-1 but no other coagulation markers such as TAT, plasmin-plasmin inhibitor complex, protein C, thrombomodulin, and soluble fibrin were associated with mortality.…”

“…Furthermore, the over-suppression of fibrinolysis caused mainly by PAI-1 constitutes an important target for therapy in patients with sepsis and DIC [ 2 ]. In the former issue of Journal of Intensive Care , Hoshino et al [ 3 ] reported the clinical significance of measuring total PAI-1 antigen in sepsis in their retrospective observational study. Here, we introduce the accumulated knowledge with respect to this issue.…”

Suspected Heparin-Induced Thrombocytopenia in a COVID-19 Patient on Extracorporeal Membrane Oxygenation Support: A Case Report.

“…However, D-Dimer are usually high in ECMO patients [11] and prolonged coagulation times are associated with anticoagulant use. Moreover, PAI-1, plasminogen, α2-antiplasmin, which are usually abnormal in sepsisrelated DIC [12,13], were within normal ranges. Therefore, DIC was unlikely in our patient.…”