Thrombomodulin is a Strong Predictor of Multiorgan Dysfunction Syndrome in Patients With Sepsis

Mihajlović, D; Lendak, Dajana; Drašković, Biljana; Mikic, Aleksandra S. Novakov; Mitić, Gorana; Ćebović, Tatjana; Brkić, Snežana

doi:10.1177/1076029613508600

Cited by 22 publications

(21 citation statements)

References 31 publications

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Section: Discussionmentioning

confidence: 99%

“…In terms of the thrombomodulin/activated protein C system, it has been shown that septic patients that develop MODS have higher levels of thrombomodulin and lower levels of protein C than patients without MODS. 22 Serum thrombomodulin levels are related to mortality and may be used in MODS monitoring in patients with sepsis. 23 Decreased protein C levels have long been recognized in patients with sepsis, especially in the presence of DIC or multiple organ failure, and have been associated with outcome.…”

Section: Adamtsmentioning

confidence: 99%

See 1 more Smart Citation

Variation of endothelium‐related hemostatic factors during sepsis

Vasileiadis

Politou

Dimopoulos³

et al. 2018

Microcirculation

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Section: Discussionmentioning

confidence: 99%

Section: Adamtsmentioning

confidence: 99%

Variation of endothelium‐related hemostatic factors during sepsis

Vasileiadis

Politou

Dimopoulos³

et al. 2018

Microcirculation

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“…Increased serum thrombomodulin levels have been reported in different sepsis syndromes and to be correlated with disease severity. Mihajlovic et al conducted a 1-year prospective study in 60 adults with sepsis and found that the serum thrombomodulin level could be used to predict the severity of sepsis, and also that it was a significant predictor of the development of MODS [ 11 ]. Lin et al conducted a prospective study in 100 adults with sepsis, and also found that serum thrombomodulin level independently predicted the development of disseminated intravascular coagulation (hazard ratio 1.13) and multiple organ dysfunction syndrome (hazard ratio 1.12) [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

“…Third, we only determined serum thrombomodulin levels and we did not analyze other biomarkers of coagulopathy or vascular injury such as protein C, protein S [ 11 ], ICAM-1, VCAM-1 and E-selectin [ 10 ]. Therefore, it is difficult to confirm the pathophysiological role of thrombomodulin in sepsis.…”

Section: Limitationsmentioning

confidence: 99%

Increased serum thrombomodulin level is associated with disease severity and mortality in pediatric sepsis

et al. 2017

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BackgroundEndothelial dysfunction plays an important role in the pathophysiology of sepsis. As previously reported, the serum thrombomodulin is elevated in diseases associated with endothelial injury.ObjectiveThe aim of this study was to investigate the association of serum thrombomodulin level in different pediatric sepsis syndromes and evaluate the relationship with disease severity and mortality.MethodsWe prospectively collected cases of sepsis treated in a pediatric intensive care unit from June 2012 to July 2015 at Chang Gung Children’s Hospital in Taoyuan, Taiwan. Clinical characteristics and serum thrombomodulin levels were analyzed.ResultsIncreased serum thrombomodulin levels on days 1 and 3 of the diagnosis of sepsis were found in different pediatric sepsis syndromes. Patients with septic shock had significantly increased serum thrombomodulin levels on days 1 and 3 [day 1: median, 6.9 mU/ml (interquartile range (IQR): 5.8–12.8) and day 3: median, 5.8 mU/ml (IQR: 4.6–10.8)] compared to healthy controls [median, 3.4 mU/ml (IQR: 2.3–4.2)] (p = <0.001 and 0.001, respectively) and those with sepsis [day 1: median, 2.9 mU/ml (IQR: 1.8–4.7) and day 3: median, 3 mU/ml (IQR: 1.5–3.5)] and severe sepsis [day 1: median, 3.3 mU/ml (IQR: 1.3–8.6) and day 3: median, 4.4 mU/ml (IQR: 0.5–6)] (p = <0.001 and 0.001, respectively). There was also a significant positive correlation between serum thrombomodulin level on day 1 and day 1 PRISM-II, PELOD, P-MOD and DIC scores. The patients who died had significantly higher serum thrombomodulin levels on days 1 and 3 [day 1: median, 9.9 mU/ml (IQR: 6.2–15.6) and day 3: median, 10.4 mU/ml (IQR: 9.2–11.7)] than the survivors [day 1; median, 4.4 mU/ml (IQR: 2.2–7.5) and day 3: [median, 3.5 mU/ml (IQR: 1.6–5.7)] (p = 0.046 and 0.012, respectively).ConclusionIncreased serum thrombomodulin levels were found in different pediatric sepsis syndromes and correlated with disease severity and mortality.

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“…Endothelial dysfunction is central to the pathogenesis of sepsis and is characterized by both macro-and microvascular dysfunction. Markers of endothelial injury are elevated in patients with sepsis and correlate with severity of illness and organ dysfunction [29][30][31]. To determine whether CFH increases endothelial injury in sepsis, we measured ICAM-1, E-selectin, and PAI-1 at 24 hours in mouse plasma ( Fig 3A-3C).…”

Section: Cfh Does Not Affect Circulating Markers Of Endothelial Injurmentioning

confidence: 99%

Cell-free hemoglobin increases inflammation, lung apoptosis, and microvascular permeability in murine polymicrobial sepsis

et al. 2020

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Increased endothelial permeability is central to the pathogenesis of sepsis and leads to organ dysfunction and death but the endogenous mechanisms that drive increased endothelial permeability are not completely understood. We previously reported that cell-free hemoglobin (CFH), elevated in 80% of patients with sepsis, increases lung microvascular permeability in an ex vivo human lung model and cultured endothelial cells. In this study, we augmented a murine model of polymicrobial sepsis with elevated circulating CFH to test the hypothesis that CFH increases microvascular endothelial permeability by inducing endothelial apoptosis. Mice were treated with an intraperitoneal injection of cecal slurry with or without a single intravenous injection of CFH. Severity of illness, mortality, systemic and lung inflammation, endothelial injury and dysfunction and lung apoptosis were measured at selected time points. We found that CFH added to CS increased sepsis mortality, plasma inflammatory cytokines as well as lung apoptosis, edema and inflammation without affecting large vessel reactivity or vascular injury marker concentrations. These results suggest that CFH is an endogenous mediator of increased endothelial permeability and apoptosis in sepsis and may be a promising therapeutic target. OPEN ACCESS Citation: Meegan JE, Shaver CM, Putz ND, Jesse JJ, Landstreet SR, Lee HNR, et al. (2020) Cell-free hemoglobin increases inflammation, lung apoptosis, and microvascular permeability in murine polymicrobial sepsis. PLoS ONE 15(2):

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Thrombomodulin is a Strong Predictor of Multiorgan Dysfunction Syndrome in Patients With Sepsis

Abstract: The level of thrombomodulin not only was able to distinguish the severity of sepsis but also was a significant predictor of MODS development.

Cited by 22 publications

References 31 publications

Variation of endothelium‐related hemostatic factors during sepsis

Variation of endothelium‐related hemostatic factors during sepsis

Increased serum thrombomodulin level is associated with disease severity and mortality in pediatric sepsis

Cell-free hemoglobin increases inflammation, lung apoptosis, and microvascular permeability in murine polymicrobial sepsis

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