scholarly journals Endothelial Dysfunction Is Associated with Mortality and Severity of Coagulopathy in Patients with Sepsis and Disseminated Intravascular Coagulation

2019 ◽  
Vol 25 ◽  
pp. 107602961985216 ◽  
Author(s):  
Amanda Walborn ◽  
Matthew Rondina ◽  
Michael Mosier ◽  
Jawed Fareed ◽  
Debra Hoppensteadt
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Protein C ◽  
High Mobility ◽  
Severity Of Illness ◽  
Endothelial Activation ◽  
Endothelial Damage ◽  
Intravascular Coagulation ◽  
Angiopoietin 2 ◽  
Von Willebrand ◽  
Relationship Of

The role of the endothelium in sepsis-associated disseminated intravascular coagulation (DIC) is multifaceted and may contribute substantially to disease severity and outcome. The purpose of this study was to quantify measures of endothelial function, including markers of activation (endocan, Angiopoietin-2 [Ang-2], and von Willebrand Factor), endogenous anticoagulants (tissue factor pathway inhibitor and protein C), and damage-associated factors (High Mobility Group Box 1 [HMGB-1]) in the plasma of patients with sepsis and DIC, and to determine the relationship of these factors with severity of illness and outcome. Plasma samples were collected from 103 adult patients with sepsis within 48 hours of intensive care unit admission. Biomarker levels were measured using commercially available, standardized methods. Disseminated intravascular coagulation was diagnosed according to the International Society of Thrombosis and Hemostasis scoring algorithm. Twenty-eight-day mortality was used as the primary end point. In this study, endothelial damage and dysfunction were associated with the severity of coagulopathy and mortality in DIC patients. Loss of the endogenous anticoagulant protein C and elevation in the vascular regulator Ang-2 were associated with the development of overt DIC. In addition to Ang-2 and protein C, endocan, a biomarker of endothelial activation, and HMGB-1, a mediator of endothelial damage and activation, were significantly associated with mortality. This underscores the contribution of the endothelium to the pathogenesis of sepsis-associated DIC.

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

2012 ◽  
Vol 59 (4) ◽  
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.

scholarly journals Safety of plasma-derived protein C for treating disseminated intravascular coagulation in adult patients with active cancer

2012 ◽  
Vol 87 (2) ◽  
pp. 230-232 ◽  
Author(s):  
Alessandra Malato ◽  
Giorgia Saccullo ◽  
Lucio Lo Coco ◽  
Clementina Caracciolo ◽  
Simona Raso ◽  
...  
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Protein C ◽  
Adult Patients ◽  
Intravascular Coagulation ◽  
Active Cancer

scholarly journals Protein C activity value as a prognostic factor in sepsis-induced disseminated intravascular coagulation

2014 ◽  
Vol 21 (6) ◽  
pp. 614-622
Author(s):  
Toshihiro Sakurai ◽  
Shu Yamada ◽  
Maki Kitada ◽  
Satoshi Hashimoto ◽  
Shoko Hashimoto ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Disseminated Intravascular Coagulation ◽  
Protein C ◽  
Intravascular Coagulation ◽  
Protein C Activity

Purpura Fulminans in a Chinese Boy With Congenital Protein C Deficiency

PEDIATRICS ◽  
1986 ◽  
Vol 77 (5) ◽  
pp. 670-676
Author(s):  
Patrick Yuen ◽  
Alfred Cheung ◽  
Hsiang Ju Lin ◽  
Faith Ho ◽  
Jun Mimuro ◽  
...  
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Protein C ◽  
Purpura Fulminans ◽  
Fresh Frozen Plasma ◽  
Protein C Deficiency ◽  
Intravascular Coagulation ◽  
The Family ◽  
Fresh Frozen ◽  
Frozen Plasma ◽  
Congenital Protein C Deficiency

Severe and recurrent purpura fulminans developed in a Chinese boy at one day of age. Results of coagulation studies performed on the patient during attacks were compatible with the diagnosis of disseminated intravascular coagulation. Subsequent investigations have revealed that the patient is homozygous and that his parents are heterozygous for protein C deficiency. Cryoprecipitate and fresh frozen plasma induced a remission, and administration of warfarin has been successful in preventing recurrence of attacks for as long as 8 months without infusion of any plasma components. None of the family members who are heterozygous for protein C deficiency have had thrombotic episodes.

scholarly journals The von Willebrand Pig as a Model for Atherosclerosis Research

1977 ◽  
Author(s):  
V. Fuster ◽  
E. J. W. Bowie ◽  
J. C. Lewis
Keyword(s):  
Arterial Wall ◽  
Fatty Infiltration ◽  
Endothelial Damage ◽  
Blue Dye ◽  
Ideal Model ◽  
Wall Interaction ◽  
Von Willebrand ◽  
Relationship Of ◽  
Atherosclerosis Research ◽  
Single Lesion

The aortas of 11 pigs with homozygous von Willebrand’s disease (vWd) were compared with those of 11 normal pigs, all aged 1 to 3 years. Six of the controls exhibited multiple arteriosclerotic plaques over 2 mm. in diameter with intimal thickenings of 63 to 130 microns. In contrast, none of the vWd pigs had multiple plaques; one had a single lesion over 2 mm. in diameter.Ten additional pigs, 5 controls and 5 with homozygous vWd, were placed on a 2% cholesterol diet for 6 months, beginning at the age of 3 months. Four of the controls developed aortic arteriosclerotic lesions exceeding 7.5% of the entire surface. Intimal thickness ranged up to 370 microns. In contrast, 4 of the vWd pigs developed lesions not exceeding 0.5% of the aortic surface; the fifth vWd pig had arteriosclerotic lesions involving 7.3% of the aortic surface.The aortas of the vWd pigs did stain with Evans blue dye injected antemortem, and they exhibited fatty infiltration in the intima. By electron microscopy, severe endothelial damage was apparent, but there was no intimal proliferation.The vWd pig seems to be an ideal model for arteriosclerosis research and the possible relationship of our findings may be related to impaired platelet-arterial wall interaction in vWd.

scholarly journals Insights Into Immunothrombosis: The Interplay Among Neutrophil Extracellular Trap, von Willebrand Factor, and ADAMTS13

2020 ◽  
Vol 11 ◽  
Author(s):  
Junxian Yang ◽  
Zhiwei Wu ◽  
Quan Long ◽  
Jiaqi Huang ◽  
Tiantian Hong ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Therapeutic Strategy ◽  
Endothelial Activation ◽  
Endothelial Damage ◽  
Neutrophil Extracellular Trap ◽  
Activated Neutrophils ◽  
A Disintegrin And Metalloproteinase ◽  
Von Willebrand ◽  
Willebrand Factor

Both neutrophil extracellular traps (NETs) and von Willebrand factor (VWF) are essential for thrombosis and inflammation. During these processes, a complex series of events, including endothelial activation, NET formation, VWF secretion, and blood cell adhesion, aggregation and activation, occurs in an ordered manner in the vasculature. The adhesive activity of VWF multimers is regulated by a specific metalloprotease ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13). Increasing evidence indicates that the interaction between NETs and VWF contributes to arterial and venous thrombosis as well as inflammation. Furthermore, contents released from activated neutrophils or NETs induce the reduction of ADAMTS13 activity, which may occur in both thrombotic microangiopathies (TMAs) and acute ischemic stroke (AIS). Recently, NET is considered as a driver of endothelial damage and immunothrombosis in COVID-19. In addition, the levels of VWF and ADAMTS13 can predict the mortality of COVID-19. In this review, we summarize the biological characteristics and interactions of NETs, VWF, and ADAMTS13, and discuss their roles in TMAs, AIS, and COVID-19. Targeting the NET-VWF axis may be a novel therapeutic strategy for inflammation-associated TMAs, AIS, and COVID-19.

scholarly journals Roles of protease-activated receptors in a mouse model of endotoxemia

Blood ◽  
2006 ◽  
Vol 107 (10) ◽  
pp. 3912-3921 ◽  
Author(s):  
Eric Camerer ◽  
Ivo Cornelissen ◽  
Hiroshi Kataoka ◽  
Daniel N. Duong ◽  
Yao-Wu Zheng ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Disseminated Intravascular Coagulation ◽  
Inflammatory Responses ◽  
Endothelial Activation ◽  
Wild Type ◽  
Protease Activated Receptors ◽  
Endotoxin Challenge ◽  
Intravascular Coagulation ◽  
Endotoxemia Model ◽  
Independent Process

Endotoxemia is often associated with extreme inflammatory responses and disseminated intravascular coagulation. Protease-activated receptors (PARs) mediate cellular responses to coagulation proteases, including platelet activation and endothelial cell reactions predicted to promote inflammation. These observations suggested that PAR activation by coagulation proteases generated in the setting of endotoxemia might promote platelet activation, leukocyte-mediated endothelial injury, tissue damage, and death. Toward testing these hypotheses, we examined the effect of PAR deficiencies that ablate platelet and endothelial activation by coagulation proteases in a mouse endotoxemia model. Although coagulation was activated as measured by thrombin-antithrombin (TAT) production and antithrombin III (ATIII) depletion, Par1–/–, Par2–/–, Par4–/–, Par2–/–:Par4–/–, and Par1–/–:Par2–/– mice all failed to show improved survival or decreased cytokine responses after endotoxin challenge compared with wild type. Thus, our results fail to support a necessary role for PARs in linking coagulation to inflammation or death in this model. Interestingly, endotoxin-induced thrombocytopenia was not diminished in Par4–/– mice. Thus, a mechanism independent of platelet activation by thrombin was sufficient to cause thrombocytopenia in our model. These results raise the possibility that decreases in platelet count in the setting of sepsis may not be caused by disseminated intravascular coagulation but instead report on a sometimes parallel but independent process.

Biochip Array Analysis of Various Mediators of Inflammation in Disseminated Intravascular Coagulation

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2302-2302 ◽  
Author(s):  
Saud Rahman ◽  
Debra Hoppensteadt ◽  
Josephine Cunanan ◽  
Rachael Davis ◽  
Nasir Sadeghi ◽  
...  
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Conflicts Of Interest ◽  
Vascular Dysfunction ◽  
Tumor Necrosis Factor Receptor ◽  
Neuron Specific Enolase ◽  
Endothelial Damage ◽  
Intravascular Coagulation ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Mediators Of Inflammation ◽  
Circulating Levels

Abstract Abstract 2302 Disseminated intravascular coagulation is a polypathologic syndrome which involves blood, endothelial and target organ dysfunction resulting in the generation of various mediators of vascular dysfunction, hemostatic aberrations and hemodynamic disturbances. In addition, various disorders of target organs such as kidney, liver, heart and brain are observed. Uncontrolled protease generation results in the formation of various mediators of inflammation such as neuron specific enolase (NSE), neutrophil gelatinase associated lipocalin (NGal) and soluble tumor necrosis factor receptor 1 (TNF R1). Endothelial damage results in the generation of thrombomodulin (TM) and endogenous coagulation/fibrinolysis results in D- Dimer formation. In order to study the circulating levels of these mediators, a Biochip array method (Randox, Oceanside, CA) was utilized with samples obtained from clinically diagnosed DIC (n=100) and normal individuals (n=10). The results are summarized in the following table. Circulating levels of these mediators were markedly increased in DIC patients in comparison to normals. The most striking increase was noted in NGal (4–6 fold) and TNF R1 (10 fold). Other mediators were also increased in the DIC group, however the data was broadly scattered. These results indicate that beside the aberration in the hemostatic system NGal and TNF R1 along with other inflammatory mediators may play a major role in the pathophysiology of DIC.MarkerNormal ControlsDIC BaselineCRP (ug/ml)3.47 + 0.913.11 + 0.2*NSE (ng/ml)6.11 + 8.610.78 + 1.6*NGAL(ng/ml)306.45 + 25.51376.56 + 48.5*TNFR1 (ng/ml)0.35 + 0.013.89 + 0.3*DD (ng/ml)232.8 + 74.41318.94 + 80.5*TM (ng/ml)3.4 + 0.33.16 + 0.2 P=<0.05 Disclosures: No relevant conflicts of interest to declare.

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