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

Alves, Brunna Eulálio; Montalvão, Silmara Aparecida de Lima; Aranha, Francisco; Lorand-Metze, Irene; Souza, Cármino Antônio de; Annichino‐Bizzacchi, Joyce Maria; Paula, Erich Vinícius De

doi:10.1186/1479-5876-9-23

Cited by 36 publications

(32 citation statements)

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“…In fact, we were not able to confirm previous reports of VEGF-A or sFlt-1 as informative biomarkers of septic shock development in patients with FN [23,32]. We speculate that these discrepancies are associated with differences in the time-point of sample collection, and with the potential influence of severe neutropenia and thrombocytopenia in the variation of VEGF-A, as neutrophils and platelets are major sources of these mediator [33].…”

Section: Discussioncontrasting

confidence: 88%

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

et al. 2013

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IntroductionEndothelial barrier breakdown is a hallmark of septic shock, and proteins that physiologically regulate endothelial barrier integrity are emerging as promising biomarkers of septic shock development. Patients with cancer and febrile neutropenia (FN) present a higher risk of sepsis complications, such as septic shock. Nonetheless, these patients are normally excluded or under-represented in sepsis biomarker studies. The aim of our study was to validate the measurement of a panel of microvascular permeability modulators as biomarkers of septic shock development in cancer patients with chemotherapy-associated FN.MethodsThis was a prospective study of diagnostic accuracy, performed in two distinct in-patient units of a university hospital. Levels of vascular endothelial growth factor A (VEGF-A), soluble fms-like tyrosine kinase-1 (sFlt-1) and angiopoietin (Ang) 1 and 2 were measured after the onset of neutropenic fever, in conditions designed to mimic the real-world use of a sepsis biomarker, based on our local practice. Patients were categorized based on the development of septic shock by 28 days as an outcome.ResultsA total of 99 consecutive patients were evaluated in the study, of which 20 developed septic shock and 79 were classified as non-complicated FN. VEGF-A and sFlt-1 levels were similar between both outcome groups. In contrast, Ang-2 concentrations were increased in patients with septic shock, whereas an inverse finding was observed for Ang-1, resulting in a higher Ang-2/Ang-1 ratio in patients with septic shock (5.29, range 0.58 to 57.14) compared to non-complicated FN (1.99, range 0.06 to 64.62; P = 0.01). After multivariate analysis, the Ang-2/Ang-1 ratio remained an independent factor for septic shock development and 28-day mortality.ConclusionsA high Ang-2/Ang-1 ratio can predict the development of septic shock in cancer patients with febrile neutropenia.

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Section: Discussioncontrasting

confidence: 88%

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

et al. 2013

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“…Increased concentrations of sFlt-1 have been shown in sepsis and have been positively associated with more severe sepsis [16,28,29,30,31]. In 2010, Shapiro et al [16] reported a strong association between sFlt-1 plasma concentrations and the severity of sepsis, as well as the development of organ dysfunction in sepsis.…”

Section: Discussionmentioning

confidence: 99%

Serum Soluble Fms-Like Tyrosine Kinase 1 (sFlt-1) Predicts the Severity of Acute Pancreatitis

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Sporek

Mazur-Laskowska³

et al. 2016

IJMS

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Organ failure is the most important determinant of the severity of acute pancreatitis (AP). Soluble fms-like tyrosine kinase 1 (sFlt-1) is positively associated with organ failure in sepsis. Our aim was to evaluate the diagnostic utility of automated sFlt-1 measurements for early prediction of AP severity. Adult patients (66) with AP were recruited, including 46 with mild (MAP), 15 with moderately-severe (MSAP) and 5 with severe AP (SAP). Serum and urine samples were collected twice. Serum sFlt-1 was measured with automated electrochemiluminescence immunoassay. Serum concentrations of sFlt-1 were significantly higher in patients with MSAP and SAP as compared to MAP. SAP patients had the highest concentrations. At 24 and 48 h, sFlt-1 positively correlated with inflammatory markers (leukocyte count, C-reactive protein), kidney function (creatinine, urea, cystatin C, serum and urine neutrophil gelatinase-associated lipocalin, urine albumin/creatinine ratio), D-dimer and angiopoietin-2. sFlt-1 positively correlated with the bedside index of severity in AP (BISAP) score and the duration of hospital stay. Serum sFlt-1 above 139 pg/mL predicted more severe AP (MSAP + SAP). In the early phase of AP, sFlt-1 is positively associated with the severity of AP and predicts organ failure, in particular kidney failure. Serum sFlt-1 may be a practical way to improve early assessment of AP severity.

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“…VEGF and VEGFR1 on the cell surface are up-regulated after endothelial injury, promoting reendothelialization by enhancing vascular remodeling [28]. These results suggest that higher sVEGFR1 levels may hamper VEGF signaling in the process of endothelial repair, thereby leading to disease progression and organ dysfunction [5,29]. Furthermore, high circulating sVRGFR1 levels correlate with morbidity and mortality, and are a potent marker of disease severity in septic or critically ill patients [5,26].…”

Section: Discussionmentioning

confidence: 99%

The role of angiogenic factors and their soluble receptors in acute lung injury (ALI)/ acute respiratory distress syndrome (ARDS) associated with critical illness

et al. 2013

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BackgroundAcute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are characterized by a disruption of the endothelium and alveolar epithelial barriers involving increased microvascular permeability, thus resulting in the set of protein-rich pulmonary edema. Angiogenic factors and their receptors, including vascular endothelial growth factor (VEGF)/VEGF-receptor (VEGFR) and the angiopoietin (Ang)/Tie2 signaling pathways, play pivotal roles in both angiogenesis and microvascular permeability. The aim of the study was to assess the relationship between angiogenic factors, their soluble receptors and ALI/ARDS associated with critically ill patients, including sepsis, severe trauma, and post-cardiac arrest syndrome (PCAS).MethodsOne hundred fifty-nine critically ill patients, including 50 patients with sepsis, 57 patients with severe trauma and 52 resuscitated after out-of-hospital cardiac arrest, were divided into three subgroups: including 25 ALI patients, 101 ARDS patients and 22 non-ALI/ARDS patients. The serum levels of angiogenic factors were measured at the time of admission (day 1), as well as day 3 and day 5 and then were compared among the ALI, ARDS and non-ALI/ARDS groups. Their predictive values for developing ALI/ARDS and 28-day mortality were evaluated.ResultsHigher levels of sVEGFR1 and Ang2 were observed in the ALI and ARDS patients than in the non-ALI/ARDS patients during the entire study period. The Ang2/Ang1 ratio in the ARDS group was also significantly higher than that in the non-ALI/ADRS group. The sVEGFR2 levels in the ARDS group on day 1 were significantly lower than those of the non-ALI/ADRS group. In addition, significant positive correlations were seen between the sVEGFR1, Ang2, Ang2/Ang1, and the development of ALI/ARDS in critical illness. There were also significant negative correlations between the minimal value of sVEGFR2, the maximal value of Ang1 and the ALI/ARDS group. In particular, sVEGFR2 and Ang2 were independent predictors of developing ALI/ARDS. Moreover, Ang2 and sVEGFR2 also independently predicted the mortality in ALI/ARDS patients.ConclusionsAngiogenic factors and their soluble receptors, particularly sVEGFR2 and Ang2, are thus considered to be valuable predictive biomarkers in the development of ALI/ARDS associated with critical illness and mortality in ALI/ARDS patients.

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

Cited by 36 publications

References 31 publications

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

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

Serum Soluble Fms-Like Tyrosine Kinase 1 (sFlt-1) Predicts the Severity of Acute Pancreatitis

The role of angiogenic factors and their soluble receptors in acute lung injury (ALI)/ acute respiratory distress syndrome (ARDS) associated with critical illness

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