Open Access Highly Accessed Research article

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

Brunna E Alves1, Silmara AL Montalvao1, Franciso JP Aranha1, Tania FG Siegl1, Carmino A Souza2, Irene Lorand-Metze2, Joyce M Annichino-Bizzacchi2 and Erich V De Paula1*

Author Affiliations

1 Hematology and Hemotherapy Center, University of Campinas, Campinas, SP, Brazil

2 Faculty of Medical Sciences, University of Campinas, Campinas, SP, Brazil

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BMC Infectious Diseases 2010, 10:143  doi:10.1186/1471-2334-10-143

Published: 28 May 2010



Febrile 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.


We 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.


Patients 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.


Our 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.