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

被引:27
作者
Alves, Brunna E. [1 ]
Montalvao, Silmara A. L. [1 ]
Aranha, Franciso J. P. [1 ]
Siegl, Tania F. G. [1 ]
Souza, Carmino A. [2 ]
Lorand-Metze, Irene [2 ]
Annichino-Bizzacchi, Joyce M. [2 ]
De Paula, Erich V. [1 ]
机构
[1] Univ Estadual Campinas, Hematol & Hemotherapy Ctr, Campinas, SP, Brazil
[2] Univ Estadual Campinas, Fac Med Sci, Campinas, SP, Brazil
基金
巴西圣保罗研究基金会;
关键词
EXCESS CIRCULATING ANGIOPOIETIN-2; MULTINATIONAL-ASSOCIATION; SUPPORTIVE-CARE; ORGAN FAILURE; SEVERE SEPSIS; RISK-INDEX; DYSFUNCTION; GUIDELINES; MORTALITY;
D O I
10.1186/1471-2334-10-143
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Background: 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. Methods: 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. Results: 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. Conclusions: 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.
引用
收藏
页数:10
相关论文
共 32 条
[1]   DEFINITIONS FOR SEPSIS AND ORGAN FAILURE AND GUIDELINES FOR THE USE OF INNOVATIVE THERAPIES IN SEPSIS [J].
BONE, RC ;
BALK, RA ;
CERRA, FB ;
DELLINGER, RP ;
FEIN, AM ;
KNAUS, WA ;
SCHEIN, RMH ;
SIBBALD, WJ .
CHEST, 1992, 101 (06) :1644-1655
[2]  
Cherif H, 2006, HAEMATOL-HEMATOL J, V91, P215
[3]   Molecular mechanisms of blood vessel growth [J].
Conway, EM ;
Collen, D ;
Carmeliet, P .
CARDIOVASCULAR RESEARCH, 2001, 49 (03) :507-521
[4]   Link between coagulation abnormalities and microcirculatory dysfunction in critically ill patients [J].
De Backer, Daniel ;
Donadello, Katia ;
Favory, Raphael .
CURRENT OPINION IN ANESTHESIOLOGY, 2009, 22 (02) :150-154
[5]   Febrile Neutropenia Evolving Strategies [J].
Ellis, Michael .
RECENT ADVANCES IN CLINICAL ONCOLOGY, 2008, 1138 :329-350
[6]   The Tie-2 ligand angiopoietin-2 is stored in and rapidly released upon stimulation from endothelial cell Weibel-Paladebodies [J].
Fiedler, U ;
Scharpfenecker, M ;
Koidl, S ;
Hegen, A ;
Grunow, V ;
Schmidt, JM ;
Kriz, W ;
Thurston, G ;
Augustin, HG .
BLOOD, 2004, 103 (11) :4150-4156
[7]   Angiopoietin-2 sensitizes endothelial cells to TNF-α and has a crucial role in the induction of inflammation [J].
Fiedler, U ;
Reiss, Y ;
Scharpfenecker, M ;
Grunow, V ;
Koidl, S ;
Thurston, G ;
Gale, NW ;
Witzenrath, M ;
Rosseau, S ;
Suttorp, N ;
Sobke, A ;
Herrmann, M ;
Preissner, KT ;
Vajkoczy, P ;
Augustin, HG .
NATURE MEDICINE, 2006, 12 (02) :235-239
[8]   Admission angiopoietin levels in children with septic shock [J].
Giuliano, John S., Jr. ;
Lahni, Patrick M. ;
Harmon, Kelli ;
Wong, Hector R. ;
Doughty, Lesley A. ;
Carcillo, Joseph A. ;
Zingarelli, Basilia ;
Sukhatme, Vikas P. ;
Parikh, Samir M. ;
Wheeler, Derek S. .
SHOCK, 2007, 28 (06) :650-654
[9]   Prophylactic antibiotics or G-CSF for the prevention of infections and improvement of survival in cancer patients undergoing chemotherapy [J].
Herbst, Christine ;
Naumann, Frauke ;
Kruse, Eva-Brigitta ;
Monsef, Ina ;
Bohlius, Julia ;
Schulz, Holger ;
Engert, Andreas .
COCHRANE DATABASE OF SYSTEMATIC REVIEWS, 2009, (01)
[10]   Medical progress: The pathophysiology and treatment of sepsis. [J].
Hotchkiss, RS ;
Karl, IE .
NEW ENGLAND JOURNAL OF MEDICINE, 2003, 348 (02) :138-150