Serial changes in neutrophil–endothelial activation markers during the course of sepsis associated with disseminated intravascular coagulation

Gando, Satoshi; Koyama, Takashi; Matsuda, Naoyuki; Hayakawa, Mineji; Hoshino, Hirokatsu; Kato, Hirokatsu

doi:10.1016/j.thromres.2004.09.022

Cited by 55 publications

(45 citation statements)

References 37 publications

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“…This temporal association may represent a pathophysiological link between early leukocyte activation and subsequent endothelial release of sTM. This pattern of association is similar to previous studies that found that neutrophil products cleave TM from endothelial cell membrane [8,[11][12][13], loss of surface TM coupled with poorly regulated tissue factor activity changes the endothelium to a more procoagulant inflammatory surface, increaseing at the same time the amount of sTM release into the plasma [13]. TM is normally expressed on the endothelial cell surface bound to the endothelium.…”

Section: Discussionsupporting

confidence: 89%

“…Proinflammatory cytokines promote the synthesis and up-regulation of adhesion molecules, leading to adherence of neutrophils and activation of the endothelium. After adherence, neutrophils secrete several enzymes, such as myeloperoxidase and elastase, which cause endothelial injury [8,17]. Moreover, previous reports showed that cardiopulmonary bypass can increase plasma levels of sTM, specially under hypothermic CPBP.…”

Section: Discussionmentioning

confidence: 99%

“…In all these conditions, sTM has been associated with increased mortality [5][6][7]. Therefore, it has been suggested that the elevation of sTM levels might be associated with a higher inflammatory state [4,8,9]. Cardiac surgery with cardiopulmonary bypass (CPBP) is associated with a systemic inflammatory response similar to that observed in all these conditions, and leukocytosis with neutrophilia frequently occurs in this scenario [10].…”

Section: Introductionmentioning

confidence: 99%

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Soluble Thrombomodulin Levels are Related to Inflammation after Coronary Bypass Surgery

Arazi¹

2011

J Clinic Experiment Cardiol

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Background: Soluble Thrombomodulin (sTM) is released from endothelial cells after injury by activated leukocytes in inflammatory states and it has been associated with worse prognosis in inflammatory conditions. The purpose of this study was to analyze the association between levels of sTM and inflammation and to describe the possible explanations about association between sTM and post-operative complications. Methods and Materials:We measured levels of sTM, IL6 and leukocytes in different moments during the first month in 18 patients after coronary by-pass graft surgery. Chisquare test and Fisher test were used for categorical variables. For continuous variables we used either Student t test or Wilcoxon rank-sum test depending on whether the data were normally distributed. Results:The levels of sTM increased during the first post-surgery week, and then decreased to values similar to those recorded pre-operatively. IL6 peaked at after 24 hours, and significantly correlated with white blood cell count (Spearman 0.69, p=<0.0001). There was a significant association between sTM at T3 and white blood cells count at T1 (p=0.01224). Two patients had three or more post-operative complications, and they presented higher levels of sTM. Conclusions:We found a transient increase in sTM during the first week after CABG associated with an inflammatory response and leukocytosis. These changes could imply endothelial dysfunction after surgery and may represent prognostic factors for outcomes.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Soluble Thrombomodulin Levels are Related to Inflammation after Coronary Bypass Surgery

Arazi¹

2011

J Clinic Experiment Cardiol

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“…Loss of membrane-bound thrombomodulin into the soluble pool is thought to be caused by mechanical disruption, neutrophil-derived proteases and by rhomboids, a family of intramembranous proteases (Lohi et al 2004). Quantification of sthrombomodulin has been previously used to measure endothelial damage from a variety of causes, including hypertension, atherosclerosis, percutaneous transluminal coronary angioplasty and vasculitis (Boffa and Karmochkine 1998;Chao et al 2004;Dohi et al 2003;Gando et al 2004Gando et al ,2005Hjerkinn et al 2005;Sakamaki et al 2003).…”

Section: Rabbit S-thrombomodulin Elisamentioning

confidence: 99%

Vascular lesions and s-thrombomodulin concentrations from auricular arteries of rabbits infused with microbubble contrast agent and exposed to pulsed ultrasound

Zachary

Blue

Miller

et al. 2006

Ultrasound in Medicine & Biology

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Arterial injury resulting from the interaction of contrast agent (CA) with ultrasound (US) was studied in rabbit auricular arteries and assessed by histopathologic evaluation and s-thrombomodulin concentrations. Three sites on each artery were exposed (2.8 MHz, 5-min exposure duration, 10-Hz pulse repetition frequency, 1.4-μs pulse duration) using one of three in situ peak rarefactional pressures (0.85, 3.9 or 9.5 MPa). Saline, saline/CA, and saline/US infusion groups (n = 28) did not have histopathologic damage. The saline/CA/US infusion group (n = 10) at exposure conditions below the FDA mechanical index limit of 1.9 did not have histopathologic damage, whereas the saline/CA/US infusion group (n = 9) at exposure conditions above the FDA limit did have damage (5 of 9 arteries). Lesions were characteristic of acute coagulative necrosis. Mean s-thrombomodulin concentrations, a marker for endothelial cell injury, were highest in rabbits exposed to US at 0.85 and 3.9 MPa, suggesting that vascular injury may be physiological and not accompanied by irreversible cellular injury.

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“…TM expressed on endothelial cell surface is cleaved by various proteases produced by activated immune cells under the process of endothelial injury. 24,25 Plasma levels of TM were correlated with the severity of endothelial damage. 21 Elevation of plasma levels of TM and FDP were successfully improved by the use of rTM (Figure 2).…”

Section: Discussionmentioning

confidence: 99%

Thrombomodulin alleviates murine GVHD in association with an increase in the proportion of regulatory T cells in the spleen

Ikezoe

Yang

Nishioka

et al. 2014

Bone Marrow Transplant

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Recombinant human soluble thrombomodulin (rTM), a potent anticoagulant, has been used for the treatment of disseminated intravascular coagulation in Japan since 2008. Interestingly, rTM possesses anti-inflammatory and cytoprotective functions. This study examined whether rTM alleviates GVHD in a murine hematopoietic SCT (HSCT) model. Use of rTM significantly improved the survival of mice on day 28 of transplantation (survival rate 70% in rTM -treated mice vs 35% in control, P o0.05) in association with a significant decrease in plasma levels of IL-6, IFN-γ and high-mobility group B1 DNA-binding protein on day 7 of HSCT. Intriguingly, the proportion of regulatory T cells in the spleen was significantly increased in rTM-treated mice on day 7 of transplantation compared with control diluent-treated mice. In addition, elevated plasma levels of TM and fibrin/fibrinogen degradation product were noted in HSCT-recipient mice, suggesting coagulopathy caused by endothelial cell damage in this GVHD model. The use of rTM potently decreased these levels. Importantly, rTM did not hamper the anti-GVL and engraftment of hematopoietic cells. Taken together, the use of rTM may prevent GVHD and serve as a potential therapeutic strategy to improve clinical outcomes in individuals who receive HSCT.

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Serial changes in neutrophil–endothelial activation markers during the course of sepsis associated with disseminated intravascular coagulation

Cited by 55 publications

References 37 publications

Soluble Thrombomodulin Levels are Related to Inflammation after Coronary Bypass Surgery

Soluble Thrombomodulin Levels are Related to Inflammation after Coronary Bypass Surgery

Vascular lesions and s-thrombomodulin concentrations from auricular arteries of rabbits infused with microbubble contrast agent and exposed to pulsed ultrasound

Thrombomodulin alleviates murine GVHD in association with an increase in the proportion of regulatory T cells in the spleen

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