Autotaxin Activity Predicts 30-Day Mortality in Sepsis Patients and Correlates With Platelet Count and Vascular Dysfunction

Abstract

Objectives: We investigated whether platelet count associated with biomarkers of endothelial function, and additionally sought to identify novel predictors of outcomes in a cohort of patients with severe sepsis at a quaternary care academic medical center. Design: Prospective, observational cohort. Patients: Eighty-six sepsis patients admitted into intensive care units were prospectively enrolled into an on-site sepsis registry and biobank. Interventions: None. Measurements and Main Results: Platelet count, mean platelet volume, platelet mass, plasma angiopoietin-1 and angiopoietin-2, syndecan-1, platelet factor 4, sCD40L concentrations, and plasma autotaxin activity were determined for each patient at enrollment. Patient mortality was recorded up to 30 days following hospital discharge. Platelet count and plasma sCD40L was significantly lower in patients who did not survive up to 30 days following hospital discharge. Angiopoietin-2 and the angiopoietin-2/1 ratio were significantly higher in patients who did not survive up to 30 days following discharge. Furthermore, plasma autotaxin activity was significantly higher in patients who did not survive up to 30 days. Interestingly, autotaxin activity correlated with platelet count and the ratio of angiopoietin-2/1 across our population. Conclusions: Platelet count, the ratio of angiopoietin-2/1, and autotaxin activity all predicted 30-day mortality. Autotaxin activity within the plasma correlates with both platelet counts and vascular dysfunction biomarkers across both survivors and non-survivors indicating a possible involvement of autotaxin within sepsis.

Serum autotaxin as a novel prognostic marker in patients with non‐ischaemic dilated cardiomyopathy

“…In addition, it has been reported to be associated with vascular endothelial dysfunction and is a prognostic factor in patients with cardiogenic shock. 15,28,29 The relationship between vascular endothelial function and HF has also been reported. 23,30 Elevated ATX might also increase the levels of other inflammatory substances, which might have affected the prognosis.…”

“…14 Furthermore, high-ATX levels were reported to be a poor prognostic factor in patients with sepsis, a systemic inflammation. 15 However, little is known about the impact of ATX levels on future cardiac events in patients with NIDCM. We hypothesize that the ATX/LPA axis may be involved in the prognosis of NIDCM.…”

Commonalities Between ARDS, Pulmonary Fibrosis and COVID-19: The Potential of Autotaxin as a Therapeutic Target

“…The increased ATX levels that were detected in severe COVID-19 patients correlated with markers of endothelial dysfunction (sP-sel, sICAM) ( 61 ) that have been independently correlated in the same samples with COVID-19 mortality ( 27 ). Similarly, ATX correlated with angiopoietin-2 levels and mortality in severe septic patients ( 63 ). In support for a major role of ATX/LPA on vascular homeostasis, ATX expression and LPA signaling have been shown necessary for the embryonic development of the vascular (and neural) system in mice ( 79 – 81 ).…”

“…Increased ATX serum levels were recently reported in non-surviving ARDS patients, where ATX serum levels were shown to be an independent prognostic factor for 28 day mortality, outperforming the established SOFA/APACHE scores ( 62 ). Plasma ATX levels correlated with mortality also in a cohort of patients with severe sepsis ( 63 ), suggesting a role for ATX/LPA in systemic hyperinflammation. ATX serum levels in ARDS correlated with the increased IL-6/IL-8 serum levels ( 62 ), further supporting an interplay of ATX/LPA with inflammation, as previously suggested in breast cancer ( 64 ).…”

Autotaxin levels in serum and bronchoalveolar lavage fluid are associated with inflammatory and fibrotic biomarkers and the clinical outcome in patients with acute respiratory distress syndrome

“…ATX expression is reportedly increased in patients with chronic liver disease and a shorter overall survival time [ 15 ] and in synovial fibroblasts from patients with rheumatoid arthritis in comparison with those from healthy controls [ 16 ]. Elevated ATX activity in plasma has recently been demonstrated to predict higher 30-day mortality in patients with sepsis [ 17 ]. Oikonomou et al detected increased concentrations of ATX in a murine model of pulmonary fibrosis and in fibrotic human lungs, and genetic deletion of ATX from bronchial epithelial cells or macrophages and pharmacological inhibition of ATX can attenuate the severity of disease [ 18 , 19 ].…”