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Critical Care
Published in: Critical Care 1/2012

Open Access 01-02-2012 | Research

Clinical utility of biomarkers of endothelial activation in sepsis-a systematic review

Authors: Katharine Xing, Srinivas Murthy, W Conrad Liles, Jeffrey M Singh

Published in: Critical Care | Issue 1/2012

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Abstract

Introduction

A strong biologic rationale exists for targeting markers of endothelial cell (EC) activation as clinically informative biomarkers to improve diagnosis, prognostic evaluation or risk-stratification of patients with sepsis.

Methods

The objective was to review the literature on the use of markers of EC activation as prognostic biomarkers in sepsis. MEDLINE was searched for publications using the keyword 'sepsis' and any of the identified endothelial-derived biomarkers in any searchable field. All clinical studies evaluating markers reflecting activation of ECs were included. Studies evaluating other exogenous mediators of EC dysfunction and studies of patients with malaria and febrile neutropenia were excluded.

Results

Sixty-one studies were identified that fulfilled the inclusion criteria. Overall, published studies report positive correlations between multiple EC-derived molecules and the diagnosis of sepsis, supporting the critical role of EC activation in sepsis. Multiple studies also reported positive associations for mortality and severity of illness, although these results were less consistent than for the presence of sepsis. Very few studies, however, reported thresholds or receiver operating characteristics that would establish these molecules as clinically-relevant biomarkers in sepsis.

Conclusions

Multiple endothelial-derived molecules are positively correlated with the presence of sepsis in humans, and variably correlated to other clinically-important outcomes. The clinical utility of these biomarkers is limited by a lack of assay standardization, unknown receiver operating characteristics and lack of validation. Additional large-scale prospective clinical trials will be required to determine the clinical utility of biomarkers of endothelial activation in the management of patients with sepsis.
Appendix
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Literature
1.
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.101.6.1644PubMed
2.
Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G: 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003, 31: 1250-1256. 10.1097/01.CCM.0000050454.01978.3BPubMed
3.
Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR: Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001, 29: 1303-1310. 10.1097/00003246-200107000-00002PubMed
4.
Biomarkers and surrogate endpoints: preferred definitions and conceptual framework Clin Pharmacol Ther 2001, 69: 89-95.
5.
6.
Hotchkiss RS, Karl IE: Endothelial cell apoptosis in sepsis: a case of habeas corpus? Crit Care Med 2004, 32: 901-902. 10.1097/01.CCM.0000115264.93926.ECPubMed
7.
Hotchkiss RS, Tinsley KW, Swanson PE, Karl IE: Endothelial cell apoptosis in sepsis. Crit Care Med 2002, 30: S225-228. 10.1097/00003246-200205001-00009PubMed
8.
Hemmer CJ, Vogt A, Unverricht M, Krause R, Lademann M, Reisinger EC: Malaria and bacterial sepsis: similar mechanisms of endothelial apoptosis and its prevention in vitro. Crit Care Med 2008, 36: 2562-2568. 10.1097/CCM.0b013e31818441eePubMed
9.
Hack CE, Zeerleder S: The endothelium in sepsis: source of and a target for inflammation. Crit Care Med 2001, 29: S21-27.PubMed
10.
Matsuda N, Teramae H, Yamamoto S, Takano K, Takano Y, Hattori Y: Increased death receptor pathway of apoptotic signaling in septic mouse aorta: effect of systemic delivery of FADD siRNA. Am J Physiol Heart Circ Physiol 2010, 298: H92-101. 10.1152/ajpheart.00069.2009PubMed
11.
Reinhart K, Bayer O, Brunkhorst F, Meisner M: Markers of endothelial damage in organ dysfunction and sepsis. Crit Care Med 2002, 30: S302-312. 10.1097/00003246-200205001-00021PubMed
12.
Schouten M, Wiersinga WJ, Levi M, van der Poll T: Inflammation, endothelium, and coagulation in sepsis. J Leukoc Biol 2008, 83: 536-545.PubMed
13.
Aird WC: The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome. Blood 2003, 101: 3765-3777. 10.1182/blood-2002-06-1887PubMed
14.
Vallet B: Bench-to-bedside review: endothelial cell dysfunction in severe sepsis: a role in organ dysfunction? Crit Care 2003, 7: 130-138. 10.1186/cc1864PubMedCentralPubMed
15.
Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, Schünemann HJ: GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008, 336: 924-926. 10.1136/bmj.39489.470347.ADPubMedCentralPubMed
16.
Trzeciak S, Jones AE, Shapiro NI, Pusateri AE, Arnold RC, Rizzuto M, Arora T, Parrillo JE, Dellinger RP, Emergency Medicine Shock Research Network (EMShockNet) investigators: A prospective multicenter cohort study of the association between global tissue hypoxia and coagulation abnormalities during early sepsis resuscitation. Crit Care Med 2010, 38: 1092-1100. 10.1097/CCM.0b013e3181cf6fbcPubMed
17.
Ganter MT, Cohen MJ, Brohi K, Chesebro BB, Staudenmayer KL, Rahn P, Christiaans SC, Bir ND, Pittet JF: Angiopoietin-2, marker and mediator of endothelial activation with prognostic significance early after trauma? Ann Surg 2008, 247: 320-326. 10.1097/SLA.0b013e318162d616PubMed
18.
Cepkova M, Brady S, Sapru A, Matthay MA, Church G: Biological markers of lung injury before and after the institution of positive pressure ventilation in patients with acute lung injury. Critical Care 2006, 10: R126. 10.1186/cc5037PubMedCentralPubMed
19.
Yano K, Liaw PC, Mullington JM, Shih SC, Okada H, Bodyak N, Kang PM, Toltl L, Belikoff B, Buras J, Simms BT, Mizgerd JP, Carmeliet P, Karumanchi SA, Aird WC: Vascular endothelial growth factor is an important determinant of sepsis morbidity and mortality. J Exp Med 2006, 203: 1447-1458. 10.1084/jem.20060375PubMedCentralPubMed
20.
Megarbane B, Marchal P, Marfaing-Koka A, Belliard O, Jacobs F, Chary I, Brivet FG: Increased diffusion of soluble adhesion molecules in meningitis, severe sepsis and systemic inflammatory response without neurological infection is associated with intrathecal shedding in cases of meningitis. Intensive Care Med 2004, 30: 867-874. 10.1007/s00134-004-2253-1PubMed
21.
Fujimi S, Ogura H, Tanaka H, Koh T, Hosotsubo H, Nakamori Y, Kuwagata Y, Shimazu T, Sugimoto H: Activated polymorphonuclear leukocytes enhance production of leukocyte microparticles with increased adhesion molecules in patients with sepsis. J Trauma 2002, 52: 443-448. 10.1097/00005373-200203000-00005PubMed
22.
Poeze M, Ramsay G, Buurman WA, Greve JW, Dentener M, Takala J: Increased hepatosplanchnic inflammation precedes the development of organ dysfunction after elective high-risk surgery. Shock 2002, 17: 451-458. 10.1097/00024382-200206000-00002PubMed
23.
Bechard D, Meignin V, Scherpereel A, Oudin S, Kervoaze G, Bertheau P, Janin A, Tonnel A, Lassalle P: Characterization of the secreted form of endothelial-cell-specific molecule 1 by specific monoclonal antibodies. J Vasc Res 2000, 37: 417-425. 10.1159/000025758PubMed
24.
Giannoudis PV, Smith RM, Banks RE, Windsor AC, Dickson RA, Guillou PJ: Stimulation of inflammatory markers after blunt trauma. Br J Surg 1998, 85: 986-990. 10.1046/j.1365-2168.1998.00770.xPubMed
25.
McGill SN, Ahmed NA, Christou NV: Increased plasma von Willebrand factor in the systemic inflammatory response syndrome is derived from generalized endothelial cell activation. Crit Care Med 1998, 26: 296-300. 10.1097/00003246-199802000-00031PubMed
26.
Kneidinger R, Bahrami S, Redl H, Schlag G, Robinson M, Weichselbraun I, Cremer J: Evaluation of a soluble E-selectin enzyme-linked immunosorbent assay under posttraumatic conditions. J Lab Clin Med 1996, 128: 520-523. 10.1016/S0022-2143(96)90050-5PubMed
27.
Hesselvik JF, Blomback M, Brodin B, Maller R: Coagulation, fibrinolysis, and kallikrein systems in sepsis: relation to outcome. Crit Care Med 1989, 17: 724-733. 10.1097/00003246-198908000-00002PubMed
28.
van der Heijden M, van Nieuw Amerongen GP, van Hinsbergh VW, Groeneveld AB: The interaction of soluble Tie2 with angiopoietins and pulmonary vascular permeability in septic and nonseptic critically ill patients. Shock 2010, 33: 263-268. 10.1097/SHK.0b013e3181b2f978PubMed
29.
Kumpers P, Hafer C, David S, Hecker H, Lukasz A, Fliser D, Haller H, Kielstein JT, Faulhaber-Walter R: Angiopoietin-2 in patients requiring renal replacement therapy in the ICU: relation to acute kidney injury, multiple organ dysfunction syndrome and outcome. Intensive Care Med 2010, 36: 462-470. 10.1007/s00134-009-1726-7PubMed
30.
Gando S, Kameue T, Matsuda N, Hayakawa M, Hoshino H, Kato H: Serial changes in neutrophil-endothelial activation markers during the course of sepsis associated with disseminated intravascular coagulation. Thromb Res 2005, 116: 91-100. 10.1016/j.thromres.2004.09.022PubMed
31.
von Heymann C, Langenkamp J, Dubisz N, von Dossow V, Schaffartzik W, Kern H, Kox WJ, Spies C: Posttraumatic immune modulation in chronic alcoholics is associated with multiple organ dysfunction syndrome. J Trauma 2002, 52: 95-103. 10.1097/00005373-200201000-00017PubMed
32.
Grad S, Ertel W, Keel M, Infanger M, Vonderschmitt DJ, Maly FE: Strongly enhanced serum levels of vascular endothelial growth factor (VEGF) after polytrauma and burn. Clin Chem Lab Med 1998, 36: 379-383. 10.1515/CCLM.1998.064PubMed
33.
Rivers EP, Kruse JA, Jacobsen G, Shah K, Loomba M, Otero R, Childs EW: The influence of early hemodynamic optimization on biomarker patterns of severe sepsis and septic shock. Crit Care Med 2007, 35: 2016-2024. 10.1097/01.CCM.0000281637.08984.6EPubMed
34.
Fang XL, Fang Q, Cai GL, Yan J: [Effect of fluid resuscitation on adhesion molecule and hemodynamics in patients with severe sepsis]. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 2006, 18: 539-541.PubMed
35.
Boldt J, Papsdorf M, Piper SN, Rothe A, Hempelmann G: Continuous heparinization and circulating adhesion molecules in the critically ill. Shock 1999, 11: 13-18.PubMed
36.
Kuang X, Ma K, Duan T: [The significance of postburn changes in plasma levels of ICAM-1, IL-10 and TNFalpha during early postburn stage in burn patients]. Zhonghua Shao Shang Za Zhi 2002, 18: 302-304.PubMed
37.
Li PJ, Yang XH, Zhang LP, Cao W, Qin J, Yao W: [Clinical significance of soluble selectins and matrix metalloproteinases-9 in patients after successful cardiopulmonary resuscitation]. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 2004, 16: 137-141.PubMed
38.
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. 10.1097/01.CCM.0000251640.77679.D7PubMed
39.
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.0b013e318188bd06PubMed
40.
Giamarellos-Bourboulis EJ, Kanellakopoulou K, Pelekanou A, Tsaganos T, Kotzampassi K: Kinetics of angiopoietin-2 in serum of multi-trauma patients: correlation with patient severity. Cytokine 2008, 44: 310-313. 10.1016/j.cyto.2008.09.003PubMed
41.
Kranidioti H, Orfanos SE, Vaki I, Kotanidou A, Raftogiannis M, Dimopoulou I, Kotsaki A, Savva A, Papapetropoulos A, Armaganidis A, Giamarellos-Bourboulis EJ: Angiopoietin-2 is increased in septic shock: evidence for the existence of a circulating factor stimulating its release from human monocytes. Immunol Lett 2009, 125: 65-71. 10.1016/j.imlet.2009.06.006PubMed
42.
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/cc7130PubMedCentralPubMed
43.
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.0030046PubMedCentralPubMed
44.
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/cc9020PubMedCentralPubMed
45.
van der Heijden M, van Nieuw Amerongen GP, Koolwijk P, van Hinsbergh VW, Groeneveld AB: Angiopoietin-2, permeability oedema, occurrence and severity of ALI/ARDS in septic and non-septic critically ill patients. Thorax 2008, 63: 903-909. 10.1136/thx.2007.087387PubMed
46.
Knaus WA, Draper EA, Wagner DP, Zimmerman JE: APACHE II: a severity of disease classification system. Crit Care Med 1985, 13: 818-829. 10.1097/00003246-198510000-00009PubMed
47.
Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca 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/BF01709751PubMed
48.
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.0b013e318206d285PubMed
49.
Ebihara I, Hirayama K, Nagai M, Kakita T, Sakai K, Tajima R, Sato C, Kurosawa H, Togashi A, Okada A, Usui J, Yamagata K, Kobayashi M: Angiopoietin balance in septic shock patients with acute lung injury: effect of direct hemoperfusion with polymyxin B-immobilized fiber. Ther Apher Dial 2011, 15: 349-354.PubMed
50.
Page AV, Kotb M, McGeer A, Low DE, Kain KC, Liles WC: Systemic dysregulation of angiopoietin-1/2 in streptococcal toxic shock syndrome. Clin Infect Dis 2011, 52: e157-161. 10.1093/cid/cir125PubMed
51.
Shapiro N, Schuetz P, Yano K, Sorasaki M, Parikh SM, Jones AE, Trzeciak S, Ngo L, Aird WC: The association of endothelial cell signaling, severity of illness, and organ dysfunction in sepsis. Crit Care 2010, 14: R182. 10.1186/cc9290PubMedCentralPubMed
52.
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.0b013e31821e4e04PubMedCentralPubMed
53.
Scherpereel A, Depontieu F, Grigoriu B, Cavestri B, Tsicopoulos A, Gentina T, Jourdain M, Pugin J, Tonnel AB, Lassalle P: Endocan, a new endothelial marker in human sepsis. Crit Care Med 2006, 34: 532-537. 10.1097/01.CCM.0000198525.82124.74PubMed
54.
Stief TW, Ijagha O, Weiste B, Herzum I, Renz H, Max M: Analysis of hemostasis alterations in sepsis. Blood Coagul Fibrinolysis 2007, 18: 179-186. 10.1097/MBC.0b013e328040bf9aPubMed
55.
Hofer S, Brenner T, Bopp C, Steppan J, Lichtenstern C, Weitz J, Bruckner T, Martin E, Hoffmann U, Weigand MA: Cell death serum biomarkers are early predictors for survival in severe septic patients with hepatic dysfunction. Crit Care 2009, 13: R93. 10.1186/cc7923PubMedCentralPubMed
56.
Kinoshita M, Ono S, Mochizuki H: Neutrophil-related inflammatory mediators in septic acute respiratory distress syndrome. J Intensive Care Med 2002, 17: 308-316. 10.1177/0885066602238033
57.
Paterson RL, Galley HF, Dhillon JK, Webster NR: Increased nuclear factor kappa B activation in critically ill patients who die. Crit Care Med 2000, 28: 1047-1051. 10.1097/00003246-200004000-00022PubMed
58.
Weigand MA, Schmidt H, Pourmahmoud M, Zhao Q, Martin E, Bardenheuer HJ: Circulating intercellular adhesion molecule-1 as an early predictor of hepatic failure in patients with septic shock. Crit Care Med 1999, 27: 2656-2661. 10.1097/00003246-199912000-00008PubMed
59.
Kayal S, Jais JP, Aguini N, Chaudiere J, Labrousse J: Elevated circulating E-selectin, intercellular adhesion molecule 1, and von Willebrand factor in patients with severe infection. Am J Respir Crit Care Med 1998, 157: 776-784.PubMed
60.
Boldt J, Muller M, Heesen M, Papsdorf M, Hempelmann G: Does age influence circulating adhesion molecules in the critically ill? Crit Care Med 1997, 25: 95-100. 10.1097/00003246-199701000-00019PubMed
61.
Egerer K, Rohr U, Krausch D, Kox W: The circulating adhesion molecules sICAM-1 and sE-selection in patients with sepsis. Anaesthesist 1997, 46: 592-598. 10.1007/s001010050442PubMed
62.
Takakuwa T, Endo S, Inada K, Kasai T, Yamada Y, Ogawa M: Assessment of inflammatory cytokines, nitrate/nitrite, type II phospholipase A2, and soluble adhesion molecules in systemic inflammatory response syndrome. Res Commun Mol Pathol Pharmacol 1997, 98: 43-52.PubMed
63.
Boldt J, Muller M, Kuhn D, Linke LC, Hempelmann G: Circulating adhesion molecules in the critically ill: a comparison between trauma and sepsis patients. Intensive Care Med 1996, 22: 122-128. 10.1007/BF01720718PubMed
64.
Endo S, Inada K, Kasai T, Takakuwa T, Yamada Y, Koike S, Wakabayashi G, Niimi M, Taniguchi S, Yoshida M: Levels of soluble adhesion molecules and cytokines in patients with septic multiple organ failure. J Inflamm 1995, 46: 212-219.PubMed
65.
Cowley HC, Heney D, Gearing AJ, Hemingway I, Webster NR: Increased circulating adhesion molecule concentrations in patients with the systemic inflammatory response syndrome: a prospective cohort study. Crit Care Med 1994, 22: 651-657. 10.1097/00003246-199404000-00022PubMed
66.
Moss M, Gillespie MK, Ackerson L, Moore FA, Moore EE, Parsons PE: Endothelial cell activity varies in patients at risk for the adult respiratory distress syndrome. Crit Care Med 1996, 24: 1782-1786. 10.1097/00003246-199611000-00004PubMed
67.
Nakae H, Endo S, Inada K, Takakuwa T, Kasai T: Changes in adhesion molecule levels in sepsis. Res Commun Mol Pathol Pharmacol 1996, 91: 329-338.PubMed
68.
Sessler CN, Windsor AC, Schwartz M, Watson L, Fisher BJ, Sugerman HJ, Fowler AA: Circulating ICAM-1 is increased in septic shock. Am J Respir Crit Care Med 1995, 151: 1420-1427.PubMed
69.
Presterl E, Lassnigg A, Mueller-Uri P, El-Menyawi I, Graninger W: Cytokines in sepsis due to Candida albicans and in bacterial sepsis. Eur Cytokine Netw 1999, 10: 423-430.PubMed
70.
Hynninen M, Valtonen M, Markkanen H, Vaara M, Kuusela P, Jousela I, Piilonen A, Takkunen O: Interleukin 1 receptor antagonist and E-selectin concentrations: a comparison in patients with severe acute pancreatitis and severe sepsis. J Crit Care 1999, 14: 63-68. 10.1016/S0883-9441(99)90015-1PubMed
71.
Takala A, Jousela I, Jansson SE, Olkkola KT, Takkunen O, Orpana A, Karonen SL, Repo H: Markers of systemic inflammation predicting organ failure in community-acquired septic shock. Clin Sci 1999, 97: 529-538. 10.1042/CS19990073PubMed
72.
Osmanovic N, Romijn FPHTM, Joop K, Sturk A, Nieuwland R: Soluble selectins in sepsis: Microparticle-associated, but only to a minor degree. Thromb Haemost 2000, 84: 731-732.PubMed
73.
Froon AH, Bonten MJ, Gaillard CA, Greve JW, Dentener MA, de Leeuw PW, Drent M, Stobberingh EE, Buurman WA: Prediction of clinical severity and outcome of ventilator-associated pneumonia. Comparison of simplified acute physiology score with systemic inflammatory mediators. Am J Resp Crit Care Med 1998, 158: 1026-1031.PubMed
74.
Geppert A, Zorn G, Karth GD, Haumer M, Gwechenberger M, Koller-Strametz J, Heinz G, Huber K, Siostrzonek P: Soluble selectins and the systemic inflammatory response syndrome after successful cardiopulmonary resuscitation. Crit Care Med 2000, 28: 2360-2365.PubMed
75.
Simons RK, Hoyt DB, Winchell RJ, Rose RM, Holbrook T: Elevated selectin levels after severe trauma: a marker for sepsis and organ failure and a potential target for immunomodulatory therapy. J Trauma 1996, 41: 653-662. 10.1097/00005373-199610000-00010PubMed
76.
Furian T, Aguiar C, Prado K, Ribeiro RV, Becker L, Martinelli N, Clausell N, Rohde LE, Biolo A: Ventricular dysfunction and dilation in severe sepsis and septic shock: Relation to endothelial function and mortality. J Crit Care 2011, in press.
77.
Shapiro NI, Yano K, Okada H, Fischer C, Howell M, Spokes KC, Ngo L, Angus DC, Aird WC: A prospective, observational study of soluble FLT-1 and vascular endothelial growth factor in sepsis. Shock 2008, 29: 452-457. 10.1097/SHK.0b013e31815072c1PubMed
78.
Knapp S, Thalhammer F, Locker GJ, Laczika K, Hollenstein U, Frass M, Winkler S, Stoiser B, Wilfing A, Burgmann H: Prognostic value of MIP-1 alpha, TGF-beta 2, sELAM-1, and sVCAM-1 in patients with gram-positive sepsis. Clin Immunol Immunopathol 1998, 87: 139-144. 10.1006/clin.1998.4523PubMed
79.
Cummings CJ, Sessler CN, Beall LD, Fisher BJ, Best AM, Fowler AA: Soluble E-selectin levels in sepsis and critical illness. Correlation with infection and hemodynamic dysfunction. Am J Resp Crit Care Med 1997, 156: 431-437.PubMed
80.
Newman W, Beall LD, Carson CW, Hunder GG, Graben N, Randhawa ZI, Gopal TV, Wiener-Kronish J, Matthay MA: Soluble E-selectin is found in supernatants of activated endothelial cells and is elevated in the serum of patients with septic shock. J Immunol 1993, 150: 644-654.PubMed
81.
Schuetz P, Christ-Crain M, Morgenthaler NG, Struck J, Bergmann A, Muller B: Circulating precursor levels of endothelin-1 and adrenomedullin, two endothelium-derived, counteracting substances, in sepsis. Endothelium 2007, 14: 345-351. 10.1080/10623320701678326PubMedCentralPubMed
82.
Karlsson S, Pettila V, Tenhunen J, Lund V, Hovilehto S, Ruokonen E, Finnsepsis Study G: Vascular endothelial growth factor in severe sepsis and septic shock. Anesth Analg 2008, 106: 1820-1826. 10.1213/ane.0b013e31816a643fPubMed
83.
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.0000150728.91155.41PubMed
84.
Rafat N, Hanusch C, Brinkkoetter PT, Schulte J, Brade J, Zijlstra JG, van der Woude FJ, van Ackern K, Yard BA, Beck GC: Increased circulating endothelial progenitor cells in septic patients: correlation with survival. Crit Care Med 2007, 35: 1677-1684. 10.1097/01.CCM.0000269034.86817.59PubMed
85.
Piechota M, Banach M, Irzmanski R, Barylski M, Piechota-Urbanska M, Kowalski J, Pawlicki L: Plasma endothelin-1 levels in septic patients. J Intensive Care Med 2007, 22: 232-239. 10.1177/0885066607301444PubMed
86.
Weitzberg E, Lundberg JM, Rudehill A: Elevated plasma levels of endothelin in patients with sepsis syndrome. Circ Shock 1991, 33: 222-227.PubMed
87.
Pittet JF, Morel DR, Hemsen A, Gunning K, Lacroix JS, Suter PM, Lundberg JM: Elevated plasma endothelin-1 concentrations are associated with the severity of illness in patients with sepsis. Ann Surg 1991, 213: 261-264. 10.1097/00000658-199103000-00014PubMedCentralPubMed
88.
Yang K-Y, Liu K-T, Chen Y-C, Chen C-S, Lee Y-C, Perng R-P, Feng J-Y: Plasma soluble vascular endothelial growth factor receptor-1 levels predict outcomes of pneumonia-related septic shock patients: a prospective observational study. Critical Care 2011, 15: R11. 10.1186/cc9412PubMedCentralPubMed
89.
Claus RA, Bockmeyer CL, Budde U, Kentouche K, Sossdorf M, Hilberg T, Schneppenheim R, Reinhart K, Bauer M, Brunkhorst FM, Losche W: Variations in the ratio between von Willebrand factor and its cleaving protease during systemic inflammation and association with severity and prognosis of organ failure. Thromb Haemost 2009, 101: 239-247.PubMed
90.
Bockmeyer CL, Claus RA, Budde U, Kentouche K, Schneppenheim R, Losche W, Reinhart K, Brunkhorst FM: Inflammation-associated ADAMTS13 deficiency promotes formation of ultra-large von Willebrand factor. Haematologica 2008, 93: 137-140. 10.3324/haematol.11677PubMed
91.
Martin K, Borgel D, Lerolle N, Feys HB, Trinquart L, Vanhoorelbeke K, Deckmyn H, Legendre P, Diehl JL, Baruch D: Decreased ADAMTS-13 (A disintegrin-like and metalloprotease with thrombospondin type 1 repeats) is associated with a poor prognosis in sepsis-induced organ failure. Crit Care Med 2007, 35: 2375-2382. 10.1097/01.CCM.0000284508.05247.B3PubMed
92.
Garcia-Fernandez N, Montes R, Purroy A, Rocha E: Hemostatic disturbances in patients with systemic inflammatory response syndrome (SIRS) and associated acute renal failure (ARF). Thromb Res 2000, 100: 19-25. 10.1016/S0049-3848(00)00306-6PubMed
93.
Lorente JA, Garcia-Frade LJ, Landin L, de Pablo R, Torrado C, Renes E, Garcia-Avello A: Time course of hemostatic abnormalities in sepsis and its relation to outcome. Chest 1993, 103: 1536-1542. 10.1378/chest.103.5.1536PubMed
94.
Ware LB, Conner ER, Matthay MA: von Willebrand factor antigen is an independent marker of poor outcome in patients with early acute lung injury. Crit Care Med 2001, 29: 2325-2331. 10.1097/00003246-200112000-00016PubMed
95.
Hovinga JAK, Zeerleder S, Kessler P, Romani de Wit T, van Mourik JA, Hack CE, ten Cate H, Reitsma PH, Wuillemin WA, Lammle B: ADAMTS-13, von Willebrand factor and related parameters in severe sepsis and septic shock. J Thromb Haemost 2007, 5: 2284-2290. 10.1111/j.1538-7836.2007.02743.x
96.
Rubin DB, Wiener-Kronish JP, Murray JF, Green DR, Turner J, Luce JM, Montgomery AB, Marks JD, Matthay MA: Elevated von Willebrand factor antigen is an early plasma predictor of acute lung injury in nonpulmonary sepsis syndrome. J Clin Invest 1990, 86: 474-480. 10.1172/JCI114733PubMedCentralPubMed
97.
Bajaj MS, Tricomi SM: Plasma levels of the three endothelial-specific proteins von Willebrand factor, tissue factor pathway inhibitor, and thrombomodulin do not predict the development of acute respiratory distress syndrome. Intensive Care Med 1999, 25: 1259-1266. 10.1007/s001340051054PubMed
98.
Moss M, Ackerson L, Gillespie MK, Moore FA, Moore EE, Parsons PE: von Willebrand factor antigen levels are not predictive for the adult respiratory distress syndrome. Am J Respir Crit Care Med 1995, 151: 15-20.PubMed
99.
Martin GS, Mannino DM, Eaton S, Moss M: The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 2003, 348: 1546-1554. 10.1056/NEJMoa022139PubMed
100.
Sankar J, Lodha R, Kabra SK: Management of septic shock: where do we stand? Indian J Pediatr 2008, 75: 1167-1169. 10.1007/S12098-008-0241-0PubMed
101.
Yang KY, Liu KT, Chen YC, Chen CS, Lee YC, Perng RP, Feng JY: Plasma soluble vascular endothelial growth factor receptor-1 levels predict outcomes of pneumonia-related septic shock patients: a prospective observational study. Crit Care 2011, 15: R11. 10.1186/cc9412PubMedCentralPubMed
102.
Bone RC, Fisher CJ Jr, Clemmer TP, Slotman GJ, Metz CA, Balk RA: Sepsis syndrome: a valid clinical entity. Methylprednisolone Severe Sepsis Study Group. Crit Care Med 1989, 17: 389-393. 10.1097/00003246-198905000-00002PubMed
103.
Doyle RL, Szaflarski N, Modin GW, Wiener-Kronish JP, Matthay MA: Identification of patients with acute lung injury. Predictors of mortality. Am J Respir Crit Care Med 1995, 152: 1818-1824.PubMed
Metadata
Title
Clinical utility of biomarkers of endothelial activation in sepsis-a systematic review
Authors
Katharine Xing
Srinivas Murthy
W Conrad Liles
Jeffrey M Singh
Publication date
01-02-2012
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2012
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc11145

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