Time-course of sFlt-1 and VEGF-A release in neutropenic patients with sepsis and septic shock: a prospective study

• Published in: Journal of translational medicine Vol. 9; no. 1; p. 23
• Main Authors: Alves, Brunna E, Montalvao, Silmara A L, Aranha, Francisco J P, Lorand-Metze, Irene, De Souza, Carmino A, Annichino-Bizzacchi, Joyce M, De Paula, Erich V
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 03.03.2011; BioMed Central; BMC
• Subjects: Adult; Analysis; Angiogenesis; Antibiotics; Biomarkers; Chemotherapy; Design; Diagnosis; Female; Fever; Health aspects; Humans; Kinases; Male; Middle Aged; Mortality; Neutropenia - blood; Neutropenia - complications; Physiological aspects; Prognosis; Prospective Studies; Proteins; Sepsis; Septic shock; Severity of Illness Index; Shock, Septic - blood; Shock, Septic - complications; Shock, Septic - diagnosis; Statistical analysis; Time Factors; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - blood; Vascular Endothelial Growth Factor A - secretion; Vascular Endothelial Growth Factor Receptor-1 - blood; Vascular Endothelial Growth Factor Receptor-1 - secretion; Ventilation; Young Adult; Brazil
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/1479-5876-9-23

Septic shock is the most feared complication of chemotherapy-induced febrile neutropenia. So far, there are no robust biomarkers that can stratify patients to the risk of sepsis complications. The VEGF-A axis is involved in the control of microvascular permeability and has been involved in the pathogenesis of conditions associated with endothelial barrier disruption such as sepsis. sFlt-1 is a soluble variant of the VEGF-A receptor VEGFR-1 that acts as a decoy receptor down-regulating the effects of VEGF-A. In animal models of sepsis, sFlt-1 was capable to block the barrier-breaking negative effects of VEGF-A and to significantly decrease mortality. In non-neutropenic patients, sFlt-1 has been shown to be a promising biomarker for sepsis severity. We prospectively evaluated concentrations of sFlt-1 and VEGF-A at different time-points during febrile neutropenia, and evaluated the association of these levels with sepsis severity and septic shock development. Neutropenic patients that evolved with septic shock (n = 10) presented higher levels of sFlt-1 and VEGF-A measured 48 hours after fever onset than patients with non-complicated sepsis (n = 31) and levels of these biomarkers correlated with sepsis severity scores. Estimation of the diagnostic accuracy of sFlt-1 levels for the discrimination of patients that evolved to septic shock yielded promising results in our study population. Our data suggest that sFlt-1 and VEGF-A could be useful biomarkers for sepsis severity in patients with febrile neutropenia. In addition, the kinetics of sFlt-1 release in patients that evolve to septic shock suggest that the sFlt-1 could be a salvage compensatory mechanism in patients with septic shock, but that the magnitude of the sFlt-1 release observed in human sepsis is not sufficient to reproduce the beneficial anti-VEGF-A effects observed in animal models of sepsis.