High-mobility Group Box 1 Protein in Pediatric Trauma Patients With Acute Traumatic Coagulopathy or Disseminated Intravascular Coagulation

Abstract Background: Acute traumatic coagulopathy occurs in both pediatric and adult trauma patients and is associated with an increased risk of mortality. Trauma patients not only have increased risk for hemorrhagic complications, but also are at increased risk for thrombosis due to multiple factors including local tissue injury, inflammation, and immobility. The complex underlying pathophysiology of coagulation abnormalities associated with traumatic injury have yet to be fully elucidated. Additionally, there are significant differences in the hemostatic system of pediatric patients compared to adults. Objectives: The purpose of this study was to determine the levels of coagulation parameters including von Willebrand factor (VWF) antigen and ADAMTS13 activity in pediatric trauma patients and evaluate for possible association with injury severity and/or mortality. Methods: This study utilized plasma specimens collected from pediatric trauma patients that presented to our institution over a 2-year time period. The specimens were collected at initial presentation and 24 hours later. The injury severity was estimated using both the Glasgow Coma Scale (GCS) and Injury Severity Score (ISS). A cohort of control samples was obtained from pediatric patients for elective surgical procedures over the same time period. Plasma VWF antigen was determined by a sandwich ELISA; plasma ADAMTS13 activity was determined by FRETS-VWF73. The results were determined by nonparametric tests for the differences in median values. Results: A total of 106 trauma patient samples at initial time point, 78 trauma samples at 24 hour time point, and 54 control samples were obtained and utilized for study. There were statistically significant differences (p<0.05) in the plasma levels of VWF antigen, ADAMTS13 activity, and the ratio of ADAMTS13 activity to VWF antigen for the trauma patient samples at initial presentation when compared to controls (Table 1). At 24 hours, there were still statistically significant differences between ADAMTS13 activity and the ratio of ADAMTS13 activity to VWF antigen in trauma patients compared to controls, but there was no significant difference in VWF antigen between the two cohorts (Table 2). There was a significant difference between the decrease in ADAMTS13 activity and injury severity as estimated by ISS ³ 15 or GCS < 8 at both time points; however, ADAMTS13 activity was not statistically different in survivors vs. non-survivors. A higher VWF antigen level at initial presentation was the only factor found to be significantly different in non-survivors. Conclusions: This study demonstrates significant differences in plasma ADAMTS13 activity and VWF antigen in pediatric trauma patients compared to controls. In patients with more severe injuries as estimated by GCS and ISS, there was also a significant association with decreased levels of ADAMTS13 activity. These finding may underlie part of the prothrombotic propensity in microcirculation that occurs in patients post-trauma. Further investigation is warranted to better understand the mechanisms of acute traumatic coagulopathy and potential prognostic factors, and to determine the most effective interventions for acute traumatic coagulopathy in the pediatric population. Disclosures Zheng: Ablynx: Consultancy; Alexion: Research Funding.

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Plasma Levels of High Mobility Group Box Protein in Patients with Organ Failure, Disseminated Intravascular Coagulation or Poor Outcome.

Blood ◽

10.1182/blood.v106.11.2142.2142 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2142-2142

Author(s):

Hideo Wada ◽

Tsutomu Nobori ◽

Shingo Yamada ◽

Ikuro Maruyama

Keyword(s):

Infectious Diseases ◽

Organ Failure ◽

Disseminated Intravascular Coagulation ◽

Plasma Levels ◽

High Mobility ◽

High Mobility Group ◽

Study Group ◽

Chromosomal Protein ◽

Intravascular Coagulation ◽

Significant Difference

Abstract High Mobility Group Box chromosomal protein 1 (HMGB1) is a nuclear DNA-binding protein acting as a proinflammatory cytokine when released in the extracellular space from necrotic cells, activated macrophages and dendritic cells. HMGB1 acts on a specific receptor, RAGE (receptor for advanced glycation end-products), and induces prolonged inflammation, organ failure, septicaemia and death. The aim of the study was to determine the diagnostic value of plasma HMGB1 concentration and its role in the development of organ failure in patients with disseminated intravascular coagulation (DIC). Plasma HMGB-1 levels were measured in patients with suspected DIC by ELISA and their relationships with DIC, organ failure and clinical outcome were determined. The study group included 201 patients suspected of having DIC (79 females and 122 males, age; 52.1±16.5 years, mean±SD). The study group represented all such patients admitted to the Second Department of Internal Medicine and Intensive Care Unit (ICU) of Mie University Hospital between January 1, 2002 and December 31, 2003. The underlying diseases were infectious diseases (n=40), hematopoietic diseases (n=58), solid cancers (n=16), trauma (n=21), aneurysm (n=12), autoimmune diseases (n=8), liver diseases (n=7), post-operation (n=32) and other diseases (n=7). Results: Plasma HMGB1 was below the detection limit in normal subjects, but moderately elevated in patients with infectious diseases (4.54 ± 8.18 ng/ml, mean±SD), malignancies (2.15 ± 5.34 ng/ml), and traumas (6.47 ± 13.13 ng/ml). DIC was associated with significantly high plasma HMGB1 (14.05 ± 12.56 ng/ml) in these patients. The highest HMGBI levels were in patients with organ failure (8.29 ± 10.99 ng/ml) and non-survivors (16.58 ± 11.01 ng/ml). HMGB1 plasma levels correlated with the DIC score and sepsis-related organ failure assessment (SOFA) score. Plasma levels of HMGB1 were significantly higher in patients with PAI-I of >50 ng/ml (3.66 ± 6.36 ng/ml) than in those with PAI-I <50 ng/ml (1.38 ± 2.97 ng/ml) (p< 0.05) but there was no significant difference in HMGB1 levels between patients with TNF-a of >1.5 (3.04 ± 5,56 ng/ml) and those with less than 1.5 pg/ml (2.44 ± 5.36 ng/ml). Our data suggest that HMGB-1 is a potentially suitable prognostic marker of OF or DIC.

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Plasma concentrations and importance of high mobility group box protein in the prognosis of organ failure in patients with disseminated intravascular coagulation

Thrombosis and Haemostasis ◽

10.1160/th05-05-0316 ◽

2005 ◽

Vol 94 (11) ◽

pp. 975-979 ◽

Cited By ~ 131

Author(s):

Tsuyoshi Hatada ◽

Tsutomu Nobori ◽

Kazuhiro Okabayashi ◽

Kazuo Maruyama ◽

Yasunori Abe ◽

...

Keyword(s):

Organ Failure ◽

Disseminated Intravascular Coagulation ◽

Nuclear Dna ◽

Advanced Glycation Endproducts ◽

Plasma Concentrations ◽

High Mobility ◽

Care Facility ◽

High Mobility Group ◽

Chromosomal Protein ◽

Intravascular Coagulation

SummaryHigh Mobility Group Box chromosomal protein 1 (HMGB1) is a nuclear DNA-binding protein acting as a proinflammatory cytokine when released in the extracellular space from necrotic cells, activated macrophages and dendritic cells. HMGB1 acts on a specific receptor, RAGE (receptor for advanced glycation endproducts), and induces prolonged inflammation, organ failure, septicaemia and death. The aim of the study was to determine the diagnostic value of plasma HMGB1 concentration and its role in the development of organ failure in patients with disseminated intravascular coagulation (DIC). Plasma HMGB-1 levels were measured in patients with suspected DIC and their relationships with DIC, organ failure and clinical outcome were determined. The study took place at the intensive care facility, Mie University School of Medicine and comprised 201 patients with suspected DIC. Plasma HMGB1 was below the detection limit in normal subjects, but moderately elevated in patients with infectious diseases (4.54 ± 8.18 ng/ml, mean±SD), malignancies (2.15 ± 5.34 ng/ml), and traumas (6.47 ± 13.13 ng/ml). DIC was associated with significantly high plasma HMGB1 (14.05 ± 12.56 ng/ml) in these patients. The highest HMGBI levels were in patients with organ failure (8.29 ± 10.99 ng/ml) and non-survivors (16.58 ± 11.01 ng/ml). HMGB1 plasma levels correlated with the DIC score and sepsis-related organ failure assessment (SOFA) score. In conclusion, our data suggest that HMGB-1 is a potentially suitable prognostic marker of OF or DIC.

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High mobility group B1 levels in sepsis and Disseminated Intravascular Coagulation.

Acta Biochimica Polonica ◽

10.18388/abp.2012_2092 ◽

2012 ◽

Vol 59 (4) ◽

Cited By ~ 3

Author(s):

Zeynep M Eskici ◽

Şerefden Açıkgöz ◽

Nihal Pişkin ◽

Görkem Mungan ◽

Murat Can ◽

...

Keyword(s):

Tract Infection ◽

Disseminated Intravascular Coagulation ◽

Protein C ◽

High Mobility ◽

Protein S ◽

High Mobility Group ◽

Hmgb1 Protein ◽

Intravascular Coagulation ◽

The Difference ◽

D Dimer

Cytokines trigger coagulant and fibrinolytic systems in sepsis to result in Disseminated Intravascular Coagulation (DIC) that is an important complication and leads to disseminated hemorrhages and multi-organ failure. High Mobility Group B1 DNA Binding (HMGB1) protein is a cytokine taking part in systemic inflammatory response. The objective of this study was to investigate HMGB1 levels in groups of septic patients with and without DIC.Twenty-one septic patients without DIC and 12 septic patients with DIC from the Intensive Care Unit (ICU) were included in the study. In addition, 20 patients admitted to the ICU without sepsis or DIC and 20 healthy volunteers served as controls. Levels of HMGB1, prothrombin time, activated partial thromboplastin time, fibrinogen, D-dimer, protein C, protein S, anti-thrombin III (ATIII), platelet (thrombocyte) and leukocyte count were determined. Levels of fibrinogen, protein C, ATIII and platelet count were significantly lower and D-dimer was significantly higher in the group with sepsis plus DIC compared to the group with sepsis without DIC. Levels of HMGB1 were higher in the group with sepsis and DIC compared to the group with sepsis; however, the difference was not statistically significant and the levels of HGMB1 of both groups were significantly higher compared to ICU and healthy control groups. HMGB1 levels were not significantly different in survivor and non survivor patients. HMGB1 levels did not differ in lower respiratory tract infection (LRTI) and urinary tract infection (UTI) in regard to the etiology of sepsis.

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