Imbalances in serum angiopoietin concentrations are early predictors of septic shock development in patients with post chemotherapy febrile neutropenia

Abstract

BackgroundFebrile neutropenia carries a high risk of sepsis complications, and the identification of biomarkers capable to identify high risk patients is a great challenge. Angiopoietins (Ang -) are cytokines involved in the control microvascular permeability. It is accepted that Ang-1 expression maintains endothelial barrier integrity, and that Ang-2 acts as an antagonizing cytokine with barrier-disrupting functions in inflammatory situations. Ang-2 levels have been recently correlated with sepsis mortality in intensive care units.MethodsWe prospectively evaluated concentrations of Ang-1 and Ang-2 at different time-points during febrile neutropenia, and explored the diagnostic accuracy of these mediators as potential predictors of poor outcome in this clinical setting before the development of sepsis complications.ResultsPatients that evolved with septic shock (n = 10) presented higher levels of Ang-2 measured 48 hours after fever onset, and of the Ang-2/Ang-1 ratio at the time of fever onset compared to patients with non-complicated sepsis (n = 31). These levels correlated with sepsis severity scores.ConclusionsOur data suggest that imbalances in the concentrations of Ang-1 and Ang-2 are independent and early markers of the risk of developing septic shock and of sepsis mortality in febrile neutropenia, and larger studies are warranted to validate their clinical usefulness. Therapeutic strategies that manipulate this Ang-2/Ang-1 imbalance can potentially offer new and promising treatments for sepsis in febrile neutropenia.

A high angiopoietin-2/angiopoietin-1 ratio is associated with a high risk of septic shock in patients with febrile neutropenia

“…So, it is conceivable that differences in Ang-2 levels present before chemotherapy, which have been shown to be associated with disease-free survival in high-risk myeloid malignancies [42], might have influenced our results. Arguing against this possibility is the fact that we and others have not found significant differences in pre-chemotherapy Ang-2 levels between different disease groups, even in cancers with significant angiogenic activity, such as multiple myeloma [22,42]. A third limitation refers to the importance of the SOFA score as a readout of systemic organ failure in our population, since thrombocytopenia was the only category in which 61% of our patients scored, most of them with high scores.…”

Angiopoietin 2 mediates microvascular and hemodynamic alterations in sepsis

“…Recent evidence suggests that increased destabilization and vascular regression in adult organisms occur by ANG2/TIE2-mediated phosphorylation of Ser910 of focal adhesion kinase (6,7). ANG2 was shown to be upregulated in a variety of disease entities linked to systemic inflammation, hyperpermeability, and vessel destabilization: renal failure in patients with multiorgan disease, pulmonary leakiness leading to adult respiratory distress syndrome, and sepsis development have all been linked to increased ANG2 levels circulating in the blood (8)(9)(10)(11). These findings raise the possibility that excess ANG2 critically affects the cardiovascular homeostasis during sepsis by disturbing the microvascular architecture, potentially by impairing endothelial/pericyte interaction.…”

Oxidative Stress as Marker of Sepsis in Onco Hematological Patients: A Pilot Study

“…The available data on oxidative status in haematological patients consist on limited series lacking sequential evaluation during diseaserelated events [1,6]. Sepsis, which is a leading cause of death in critically ill patients, is a complex inflammatory syndrome with a wide spectrum of severity.…”