Skip to main content
Top
Published in: Critical Care 4/2013

Open Access 01-08-2013 | Research

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

Authors: Maiara Marx Luz Fiusa, Carolina Costa-Lima, Gleice Regina de Souza, Afonso Celso Vigorito, Francisco Jose Penteado Aranha, Irene Lorand-Metze, Joyce M Annichino-Bizzacchi, Carmino Antonio de Souza, Erich V De Paula

Published in: Critical Care | Issue 4/2013

Login to get access

Abstract

Introduction

Endothelial 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.

Methods

This 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.

Results

A 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.

Conclusions

A high Ang-2/Ang-1 ratio can predict the development of septic shock in cancer patients with febrile neutropenia.
Appendix
Available only for authorised users
Literature
1.
go back to reference McMillan DC: Systemic inflammation, nutritional status and survival in patients with cancer. Curr Opin Clin Nutr Metab Care 2009, 12: 223-226. 10.1097/MCO.0b013e32832a7902PubMedCrossRef McMillan DC: Systemic inflammation, nutritional status and survival in patients with cancer. Curr Opin Clin Nutr Metab Care 2009, 12: 223-226. 10.1097/MCO.0b013e32832a7902PubMedCrossRef
2.
go back to reference Kumar G, Kumar N, Taneja A, Kaleekal T, Tarima S, McGinley E, Jimenez E, Mohan A, Khan RA, Whittle J, Jacobs E, Nanchal R, Milwaukee Initiative in Critical Care Outcomes Research Group of Investigators: Nationwide trends of severe sepsis in the 21st century (2000-2007). Chest 140: 1223-1231. Kumar G, Kumar N, Taneja A, Kaleekal T, Tarima S, McGinley E, Jimenez E, Mohan A, Khan RA, Whittle J, Jacobs E, Nanchal R, Milwaukee Initiative in Critical Care Outcomes Research Group of Investigators: Nationwide trends of severe sepsis in the 21st century (2000-2007). Chest 140: 1223-1231.
4.
go back to reference Moyer MW: New biomarkers sought for improving sepsis management and care. Nat Med 2012, 18: 999. 10.1038/nm0712-999PubMedCrossRef Moyer MW: New biomarkers sought for improving sepsis management and care. Nat Med 2012, 18: 999. 10.1038/nm0712-999PubMedCrossRef
6.
go back to reference Dejana E, Tournier-Lasserve E, Weinstein BM: The control of vascular integrity by endothelial cell junctions: molecular basis and pathological implications. Dev Cell 2009, 16: 209-221. 10.1016/j.devcel.2009.01.004PubMedCrossRef Dejana E, Tournier-Lasserve E, Weinstein BM: The control of vascular integrity by endothelial cell junctions: molecular basis and pathological implications. Dev Cell 2009, 16: 209-221. 10.1016/j.devcel.2009.01.004PubMedCrossRef
7.
go back to reference van der Flier M, van Leeuwen HJ, van Kessel KP, Kimpen JL, Hoepelman AI, Geelen SP: Plasma vascular endothelial growth factor in severe sepsis. Shock 2005, 23: 35-38. 10.1097/01.shk.0000150728.91155.41PubMedCrossRef van der Flier M, van Leeuwen HJ, van Kessel KP, Kimpen JL, Hoepelman AI, Geelen SP: Plasma vascular endothelial growth factor in severe sepsis. Shock 2005, 23: 35-38. 10.1097/01.shk.0000150728.91155.41PubMedCrossRef
8.
go back to reference Calfee CS, Gallagher D, Abbott J, Thompson BT, Matthay MA: Plasma angiopoietin-2 in clinical acute lung injury: prognostic and pathogenetic significance. Crit Care Med 2012, 40: 1731-1737. 10.1097/CCM.0b013e3182451c87PubMedPubMedCentralCrossRef Calfee CS, Gallagher D, Abbott J, Thompson BT, Matthay MA: Plasma angiopoietin-2 in clinical acute lung injury: prognostic and pathogenetic significance. Crit Care Med 2012, 40: 1731-1737. 10.1097/CCM.0b013e3182451c87PubMedPubMedCentralCrossRef
9.
go back to reference Davis JS, Yeo TW, Piera KA, Woodberry T, Celermajer DS, Stephens DP, Anstey NM: Angiopoietin-2 is increased in sepsis and inversely associated with nitric oxide-dependent microvascular reactivity. Crit Care 2010, 14: R89. 10.1186/cc9020PubMedPubMedCentralCrossRef Davis JS, Yeo TW, Piera KA, Woodberry T, Celermajer DS, Stephens DP, Anstey NM: Angiopoietin-2 is increased in sepsis and inversely associated with nitric oxide-dependent microvascular reactivity. Crit Care 2010, 14: R89. 10.1186/cc9020PubMedPubMedCentralCrossRef
10.
go back to reference Mankhambo LA, Banda DL, Jeffers G, White SA, Balmer P, Nkhoma S, Phiri H, Molyneux EM, Hart CA, Molyneux ME, Heyderman RS, Carrol ED: The role of angiogenic factors in predicting clinical outcome in severe bacterial infection in Malawian children. Crit Care 2011, 14: R91.CrossRef Mankhambo LA, Banda DL, Jeffers G, White SA, Balmer P, Nkhoma S, Phiri H, Molyneux EM, Hart CA, Molyneux ME, Heyderman RS, Carrol ED: The role of angiogenic factors in predicting clinical outcome in severe bacterial infection in Malawian children. Crit Care 2011, 14: R91.CrossRef
11.
go back to reference Ricciuto DR, dos Santos CC, Hawkes M, Toltl LJ, Conroy AL, Rajwans N, Lafferty EI, Cook DJ, Fox-Robichaud A, Kahnamoui K, Kain KC, Liaw PC, Liles WC: Angiopoietin-1 and angiopoietin-2 as clinically informative prognostic biomarkers of morbidity and mortality in severe sepsis. Crit Care Med 2011, 39: 702-710. 10.1097/CCM.0b013e318206d285PubMedCrossRef Ricciuto DR, dos Santos CC, Hawkes M, Toltl LJ, Conroy AL, Rajwans N, Lafferty EI, Cook DJ, Fox-Robichaud A, Kahnamoui K, Kain KC, Liaw PC, Liles WC: Angiopoietin-1 and angiopoietin-2 as clinically informative prognostic biomarkers of morbidity and mortality in severe sepsis. Crit Care Med 2011, 39: 702-710. 10.1097/CCM.0b013e318206d285PubMedCrossRef
12.
go back to reference Orfanos SE, Kotanidou A, Glynos C, Athanasiou C, Tsigkos S, Dimopoulou I, Sotiropoulou C, Zakynthinos S, Armaganidis A, Papapetropoulos A, Roussos C: Angiopoietin-2 is increased in severe sepsis: correlation with inflammatory mediators. Crit Care Med 2007, 35: 199-206. Erratum in: Crit Care Med 2007, 35:1224 10.1097/01.CCM.0000251640.77679.D7PubMedCrossRef Orfanos SE, Kotanidou A, Glynos C, Athanasiou C, Tsigkos S, Dimopoulou I, Sotiropoulou C, Zakynthinos S, Armaganidis A, Papapetropoulos A, Roussos C: Angiopoietin-2 is increased in severe sepsis: correlation with inflammatory mediators. Crit Care Med 2007, 35: 199-206. Erratum in: Crit Care Med 2007, 35:1224 10.1097/01.CCM.0000251640.77679.D7PubMedCrossRef
13.
go back to reference Siner JM, Bhandari V, Engle KM, Elias JA, Siegel MD: Elevated serum angiopoietin 2 levels are associated with increased mortality in sepsis. Shock 2009, 31: 348-353. 10.1097/SHK.0b013e318188bd06PubMedCrossRef Siner JM, Bhandari V, Engle KM, Elias JA, Siegel MD: Elevated serum angiopoietin 2 levels are associated with increased mortality in sepsis. Shock 2009, 31: 348-353. 10.1097/SHK.0b013e318188bd06PubMedCrossRef
14.
go back to reference van der Heijden M, Pickkers P, van Nieuw Amerongen GP, van Hinsbergh VW, Bouw MP, van der Hoeven JG, Groeneveld AB: Circulating angiopoietin-2 levels in the course of septic shock: relation with fluid balance, pulmonary dysfunction and mortality. Intensive Care Med 2009, 35: 1567-1574. 10.1007/s00134-009-1560-yPubMedPubMedCentralCrossRef van der Heijden M, Pickkers P, van Nieuw Amerongen GP, van Hinsbergh VW, Bouw MP, van der Hoeven JG, Groeneveld AB: Circulating angiopoietin-2 levels in the course of septic shock: relation with fluid balance, pulmonary dysfunction and mortality. Intensive Care Med 2009, 35: 1567-1574. 10.1007/s00134-009-1560-yPubMedPubMedCentralCrossRef
15.
go back to reference Parikh SM, Mammoto T, Schultz A, Yuan HT, Christiani D, Karumanchi SA, Sukhatme VP: Excess circulating angiopoietin-2 may contribute to pulmonary vascular leak in sepsis in humans. PLoS Med 2006, 3: e46. 10.1371/journal.pmed.0030046PubMedPubMedCentralCrossRef Parikh SM, Mammoto T, Schultz A, Yuan HT, Christiani D, Karumanchi SA, Sukhatme VP: Excess circulating angiopoietin-2 may contribute to pulmonary vascular leak in sepsis in humans. PLoS Med 2006, 3: e46. 10.1371/journal.pmed.0030046PubMedPubMedCentralCrossRef
16.
go back to reference Kumpers P, Lukasz A, David S, Horn R, Hafer C, Faulhaber-Walter R, Fliser D, Haller H, Kielstein JT: Excess circulating angiopoietin-2 is a strong predictor of mortality in critically ill medical patients. Crit Care 2008, 12: R147. 10.1186/cc7130PubMedPubMedCentralCrossRef Kumpers P, Lukasz A, David S, Horn R, Hafer C, Faulhaber-Walter R, Fliser D, Haller H, Kielstein JT: Excess circulating angiopoietin-2 is a strong predictor of mortality in critically ill medical patients. Crit Care 2008, 12: R147. 10.1186/cc7130PubMedPubMedCentralCrossRef
17.
go back to reference Giuliano JS Jr, Lahni PM, Harmon K, Wong HR, Doughty LA, Carcillo JA, Zingarelli B, Sukhatme VP, Parikh SM, Wheeler DS: Admission angiopoietin levels in children with septic shock. Shock 2007, 28: 650-654.PubMedPubMedCentral Giuliano JS Jr, Lahni PM, Harmon K, Wong HR, Doughty LA, Carcillo JA, Zingarelli B, Sukhatme VP, Parikh SM, Wheeler DS: Admission angiopoietin levels in children with septic shock. Shock 2007, 28: 650-654.PubMedPubMedCentral
18.
go back to reference Kumpers P, van Meurs M, David S, Molema G, Bijzet J, Lukasz A, Biertz F, Haller H, Zijlstra JG: Time course of angiopoietin-2 release during experimental human endotoxemia and sepsis. Crit Care 2009, 13: R64. 10.1186/cc7866PubMedPubMedCentralCrossRef Kumpers P, van Meurs M, David S, Molema G, Bijzet J, Lukasz A, Biertz F, Haller H, Zijlstra JG: Time course of angiopoietin-2 release during experimental human endotoxemia and sepsis. Crit Care 2009, 13: R64. 10.1186/cc7866PubMedPubMedCentralCrossRef
19.
go back to reference Schuetz P, Jones AE, Aird WC, Shapiro NI: Endothelial cell activation in emergency department patients with sepsis-related and non-sepsis-related hypotension. Shock 2011, 36: 104-108. 10.1097/SHK.0b013e31821e4e04PubMedPubMedCentralCrossRef Schuetz P, Jones AE, Aird WC, Shapiro NI: Endothelial cell activation in emergency department patients with sepsis-related and non-sepsis-related hypotension. Shock 2011, 36: 104-108. 10.1097/SHK.0b013e31821e4e04PubMedPubMedCentralCrossRef
20.
go back to reference Legrand M, Max A, Peigne V, Mariotte E, Canet E, Debrumetz A, Lemiale V, Seguin A, Darmon M, Schlemmer B, Azoulay E: Survival in neutropenic patients with severe sepsis or septic shock. Crit Care Med 2012, 40: 43-49. 10.1097/CCM.0b013e31822b50c2PubMedCrossRef Legrand M, Max A, Peigne V, Mariotte E, Canet E, Debrumetz A, Lemiale V, Seguin A, Darmon M, Schlemmer B, Azoulay E: Survival in neutropenic patients with severe sepsis or septic shock. Crit Care Med 2012, 40: 43-49. 10.1097/CCM.0b013e31822b50c2PubMedCrossRef
21.
go back to reference André S, Taboulet P, Elie C, Milpied N, Nahon M, Kierzek G, Billemont M, Perruche F, Charpentier S, Clément H, Pourriat JL, Claessens YE: Febrile neutropenia in French emergency departments: results of a prospective multicentre survey. Crit Care 2010, 14: R68. 10.1186/cc8972PubMedPubMedCentralCrossRef André S, Taboulet P, Elie C, Milpied N, Nahon M, Kierzek G, Billemont M, Perruche F, Charpentier S, Clément H, Pourriat JL, Claessens YE: Febrile neutropenia in French emergency departments: results of a prospective multicentre survey. Crit Care 2010, 14: R68. 10.1186/cc8972PubMedPubMedCentralCrossRef
22.
go back to reference Alves BE, Montalvao SA, Aranha FJ, Siegl TF, Souza CA, Lorand-Metze I, Annichino-Bizzacchi JM, De Paula EV: Imbalances in serum angiopoietin concentrations are early predictors of septic shock development in patients with post chemotherapy febrile neutropenia. BMC Infect Dis 2010, 10: 143. 10.1186/1471-2334-10-143PubMedPubMedCentralCrossRef Alves BE, Montalvao SA, Aranha FJ, Siegl TF, Souza CA, Lorand-Metze I, Annichino-Bizzacchi JM, De Paula EV: Imbalances in serum angiopoietin concentrations are early predictors of septic shock development in patients with post chemotherapy febrile neutropenia. BMC Infect Dis 2010, 10: 143. 10.1186/1471-2334-10-143PubMedPubMedCentralCrossRef
23.
go back to reference Alves BE, Montalvao SA, Aranha FJ, Lorand-Metze I, De Souza CA, Annichino-Bizzacchi JM, De Paula EV: Time-course of sFlt-1 and VEGF-A release in neutropenic patients with sepsis and septic shock: a prospective study. J Transl Med 2011, 9: 23. 10.1186/1479-5876-9-23PubMedPubMedCentralCrossRef Alves BE, Montalvao SA, Aranha FJ, Lorand-Metze I, De Souza CA, Annichino-Bizzacchi JM, De Paula EV: Time-course of sFlt-1 and VEGF-A release in neutropenic patients with sepsis and septic shock: a prospective study. J Transl Med 2011, 9: 23. 10.1186/1479-5876-9-23PubMedPubMedCentralCrossRef
24.
go back to reference Hughes WT, Armstrong D, Bodey GP, Bow EJ, Brown AE, Calandra T, Feld R, Pizzo PA, Rolston KV, Shenep JL, Young LS: 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis 2002, 34: 730-751. 10.1086/339215PubMedCrossRef Hughes WT, Armstrong D, Bodey GP, Bow EJ, Brown AE, Calandra T, Feld R, Pizzo PA, Rolston KV, Shenep JL, Young LS: 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis 2002, 34: 730-751. 10.1086/339215PubMedCrossRef
25.
go back to reference Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 1992, 101: 1644-1655. 10.1378/chest.101.6.1644PubMedCrossRef Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 1992, 101: 1644-1655. 10.1378/chest.101.6.1644PubMedCrossRef
26.
go back to reference Vincent JL, Moreno R, Takala J, Willatts S, De Mendonça A, Bruining H, Reinhart CK, Suter PM, Thijs LG: The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 1996, 22: 707-710. 10.1007/BF01709751PubMedCrossRef Vincent JL, Moreno R, Takala J, Willatts S, De Mendonça A, Bruining H, Reinhart CK, Suter PM, Thijs LG: The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 1996, 22: 707-710. 10.1007/BF01709751PubMedCrossRef
27.
go back to reference Klastersky J, Paesmans M, Rubenstein EB, Boyer M, Elting L, Feld R, Gallagher J, Herrstedt J, Rapoport B, Rolston K, Talcott J: The Multinational Association for Supportive Care in Cancer Risk Index: a multinational scoring system for identifying low-risk febrile neutropenic cancer patients. J Clin Oncol 2000, 18: 3038-3051.PubMed Klastersky J, Paesmans M, Rubenstein EB, Boyer M, Elting L, Feld R, Gallagher J, Herrstedt J, Rapoport B, Rolston K, Talcott J: The Multinational Association for Supportive Care in Cancer Risk Index: a multinational scoring system for identifying low-risk febrile neutropenic cancer patients. J Clin Oncol 2000, 18: 3038-3051.PubMed
28.
go back to reference Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig LM, Lijmer JG, Moher D, Rennie D, de Vet HC, Standards for Reporting of Diagnostic Accuracy: Toward complete and accurate reporting of studies of diagnostic accuracy. The STARD initiative. Am J Clin Pathol 2003, 119: 18-22. 10.1309/8EXCCM6YR1THUBAFPubMedCrossRef Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig LM, Lijmer JG, Moher D, Rennie D, de Vet HC, Standards for Reporting of Diagnostic Accuracy: Toward complete and accurate reporting of studies of diagnostic accuracy. The STARD initiative. Am J Clin Pathol 2003, 119: 18-22. 10.1309/8EXCCM6YR1THUBAFPubMedCrossRef
29.
go back to reference Klastersky J, Awada A, Paesmans M, Aoun M: Febrile neutropenia: a critical review of the initial management. Crit Rev Oncol Hematol 2011, 78: 185-194. 10.1016/j.critrevonc.2010.03.008PubMedCrossRef Klastersky J, Awada A, Paesmans M, Aoun M: Febrile neutropenia: a critical review of the initial management. Crit Rev Oncol Hematol 2011, 78: 185-194. 10.1016/j.critrevonc.2010.03.008PubMedCrossRef
30.
go back to reference Carrol ED: Angiopoietins as prognostic biomarkers and effector molecules in severe sepsis. Crit Care Med 2011, 39: 2203-2204; author reply 2204. 10.1097/CCM.0b013e31821f02bfPubMedPubMedCentralCrossRef Carrol ED: Angiopoietins as prognostic biomarkers and effector molecules in severe sepsis. Crit Care Med 2011, 39: 2203-2204; author reply 2204. 10.1097/CCM.0b013e31821f02bfPubMedPubMedCentralCrossRef
31.
go back to reference Bleeker SE, Moll HA, Steyerberg EW, Donders AR, Derksen-Lubsen G, Grobbee DE, Moons KG: External validation is necessary in prediction research: a clinical example. J Clin Epidemiol 2003, 56: 826-832. 10.1016/S0895-4356(03)00207-5PubMedCrossRef Bleeker SE, Moll HA, Steyerberg EW, Donders AR, Derksen-Lubsen G, Grobbee DE, Moons KG: External validation is necessary in prediction research: a clinical example. J Clin Epidemiol 2003, 56: 826-832. 10.1016/S0895-4356(03)00207-5PubMedCrossRef
32.
go back to reference Hamalainen S, Juutilainen A, Matinlauri I, Kuittinen T, Ruokonen E, Koivula I, Jantunen E: Serum vascular endothelial growth factor in adult haematological patients with neutropenic fever: a comparison with C-reactive protein. Eur J Haematol 2009, 83: 251-257. 10.1111/j.1600-0609.2009.01260.xPubMedCrossRef Hamalainen S, Juutilainen A, Matinlauri I, Kuittinen T, Ruokonen E, Koivula I, Jantunen E: Serum vascular endothelial growth factor in adult haematological patients with neutropenic fever: a comparison with C-reactive protein. Eur J Haematol 2009, 83: 251-257. 10.1111/j.1600-0609.2009.01260.xPubMedCrossRef
33.
go back to reference Kusumanto YH, Dam WA, Hospers GA, Meijer C, Mulder NH: Platelets and granulocytes, in particular the neutrophils, form important compartments for circulating vascular endothelial growth factor. Angiogenesis 2003, 6: 283-287.PubMedCrossRef Kusumanto YH, Dam WA, Hospers GA, Meijer C, Mulder NH: Platelets and granulocytes, in particular the neutrophils, form important compartments for circulating vascular endothelial growth factor. Angiogenesis 2003, 6: 283-287.PubMedCrossRef
34.
go back to reference Guo B, Liu Y, Tan X, Cen H: Prognostic significance of vascular endothelial growth factor expression in adult patients with acute myeloid leukemia: a meta-analysis. Leuk Lymphoma 2013, 54: 1418-1425. 10.3109/10428194.2012.748907PubMedCrossRef Guo B, Liu Y, Tan X, Cen H: Prognostic significance of vascular endothelial growth factor expression in adult patients with acute myeloid leukemia: a meta-analysis. Leuk Lymphoma 2013, 54: 1418-1425. 10.3109/10428194.2012.748907PubMedCrossRef
35.
go back to reference Tang BM, Eslick GD, Craig JC, McLean AS: Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis. Lancet Infect Dis 2007, 7: 210-217. 10.1016/S1473-3099(07)70052-XPubMedCrossRef Tang BM, Eslick GD, Craig JC, McLean AS: Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis. Lancet Infect Dis 2007, 7: 210-217. 10.1016/S1473-3099(07)70052-XPubMedCrossRef
37.
go back to reference Lukasz A, Hellpap J, Horn R, Kielstein JT, David S, Haller H, Kumpers P: Circulating angiopoietin-1 and angiopoietin-2 in critically ill patients: development and clinical application of two new immunoassays. Crit Care 2008, 12: R94. 10.1186/cc6966PubMedPubMedCentralCrossRef Lukasz A, Hellpap J, Horn R, Kielstein JT, David S, Haller H, Kumpers P: Circulating angiopoietin-1 and angiopoietin-2 in critically ill patients: development and clinical application of two new immunoassays. Crit Care 2008, 12: R94. 10.1186/cc6966PubMedPubMedCentralCrossRef
38.
go back to reference David S, Kumpers P, van Slyke P, Parikh SM: Mending leaky blood vessels: the angiopoietin-Tie2 pathway in sepsis. J Pharmacol Exp Ther 2013, 345: 2-6. 10.1124/jpet.112.201061PubMedCrossRef David S, Kumpers P, van Slyke P, Parikh SM: Mending leaky blood vessels: the angiopoietin-Tie2 pathway in sepsis. J Pharmacol Exp Ther 2013, 345: 2-6. 10.1124/jpet.112.201061PubMedCrossRef
39.
go back to reference Kovach MA, Standiford TJ: The function of neutrophils in sepsis. Curr Opin Infect Dis 2012, 25: 321-327. 10.1097/QCO.0b013e3283528c9bPubMedCrossRef Kovach MA, Standiford TJ: The function of neutrophils in sepsis. Curr Opin Infect Dis 2012, 25: 321-327. 10.1097/QCO.0b013e3283528c9bPubMedCrossRef
40.
go back to reference Alfieri A, Watson JJ, Kammerer RA, Tasab M, Progias P, Reeves K, Brown NJ, Brookes ZL: Angiopoietin-1 variant reduces LPS-induced microvascular dysfunction in a murine model of sepsis. Crit Care 2012, 16: R182. 10.1186/cc11666PubMedPubMedCentralCrossRef Alfieri A, Watson JJ, Kammerer RA, Tasab M, Progias P, Reeves K, Brown NJ, Brookes ZL: Angiopoietin-1 variant reduces LPS-induced microvascular dysfunction in a murine model of sepsis. Crit Care 2012, 16: R182. 10.1186/cc11666PubMedPubMedCentralCrossRef
41.
go back to reference Kumpers P, Gueler F, David S, Slyke PV, Dumont DJ, Park JK, Bockmeyer CL, Parikh SM, Pavenstadt H, Haller H, Shushakova N: The synthetic tie2 agonist peptide vasculotide protects against vascular leakage and reduces mortality in murine abdominal sepsis. Crit Care 2011, 15: R261. 10.1186/cc10523PubMedPubMedCentralCrossRef Kumpers P, Gueler F, David S, Slyke PV, Dumont DJ, Park JK, Bockmeyer CL, Parikh SM, Pavenstadt H, Haller H, Shushakova N: The synthetic tie2 agonist peptide vasculotide protects against vascular leakage and reduces mortality in murine abdominal sepsis. Crit Care 2011, 15: R261. 10.1186/cc10523PubMedPubMedCentralCrossRef
42.
go back to reference Kumpers P, Koenecke C, Hecker H, Hellpap J, Horn R, Verhagen W, Buchholz S, Hertenstein B, Krauter J, Eder M, David S, Göhring G, Haller H, Ganser A: Angiopoietin-2 predicts disease-free survival after allogeneic stem cell transplantation in patients with high-risk myeloid malignancies. Blood 2008, 112: 2139-2148. 10.1182/blood-2007-12-130021PubMedCrossRef Kumpers P, Koenecke C, Hecker H, Hellpap J, Horn R, Verhagen W, Buchholz S, Hertenstein B, Krauter J, Eder M, David S, Göhring G, Haller H, Ganser A: Angiopoietin-2 predicts disease-free survival after allogeneic stem cell transplantation in patients with high-risk myeloid malignancies. Blood 2008, 112: 2139-2148. 10.1182/blood-2007-12-130021PubMedCrossRef
43.
go back to reference Agrawal A, Matthay MA, Kangelaris KN, Stein J, Chu JC, Imp BM, Cortez A, Abbott J, Liu KD, Calfee CS: Plasma angiopoietin-2 predicts the onset of acute lung injury in critically ill patients. Am J Respir Crit Care Med 2013, 187: 736-742. 10.1164/rccm.201208-1460OCPubMedPubMedCentralCrossRef Agrawal A, Matthay MA, Kangelaris KN, Stein J, Chu JC, Imp BM, Cortez A, Abbott J, Liu KD, Calfee CS: Plasma angiopoietin-2 predicts the onset of acute lung injury in critically ill patients. Am J Respir Crit Care Med 2013, 187: 736-742. 10.1164/rccm.201208-1460OCPubMedPubMedCentralCrossRef
44.
go back to reference Goldenberg NM, Steinberg BE, Slutsky AS, Lee WL: Broken barriers: a new take on sepsis pathogenesis. Sci Transl Med 2011, 3: 88ps25. 10.1126/scitranslmed.3002011PubMed Goldenberg NM, Steinberg BE, Slutsky AS, Lee WL: Broken barriers: a new take on sepsis pathogenesis. Sci Transl Med 2011, 3: 88ps25. 10.1126/scitranslmed.3002011PubMed
Metadata
Title
A high angiopoietin-2/angiopoietin-1 ratio is associated with a high risk of septic shock in patients with febrile neutropenia
Authors
Maiara Marx Luz Fiusa
Carolina Costa-Lima
Gleice Regina de Souza
Afonso Celso Vigorito
Francisco Jose Penteado Aranha
Irene Lorand-Metze
Joyce M Annichino-Bizzacchi
Carmino Antonio de Souza
Erich V De Paula
Publication date
01-08-2013
Publisher
BioMed Central
Published in
Critical Care / Issue 4/2013
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc12848

Other articles of this Issue 4/2013

Critical Care 4/2013 Go to the issue