Faculty Opinions recommendation of Circulating levels of DNA-histone complex and dsDNA are independent prognostic factors of disseminated intravascular coagulation.

2017 ◽  
Author(s):  
Cheng-Hock Toh
Keyword(s):  
Prognostic Factors ◽  
Disseminated Intravascular Coagulation ◽  
Intravascular Coagulation ◽  
Circulating Levels

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.

Dysregulation of Inflammatory and Hemostatic Markers in Sepsis Associated Disseminated Intravascular Coagulation.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2223-2223 ◽  
Author(s):  
Jawed Fareed ◽  
Debra Hoppensteadt ◽  
Josephine Cunanan ◽  
Michael Mosier ◽  
Yutaka Osawa ◽  
...  
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Inflammatory Mediators ◽  
Protein C ◽  
Control Group ◽  
Functional Protein ◽  
Double Blind ◽  
Intravascular Coagulation ◽  
Hemostatic Markers ◽  
Circulating Levels ◽  
Pai 1

Abstract Abstract 2223 Disseminated intravascular coagulation (DIC) represents a complex pathophysiologic syndrome where marked alterations in the hemostatic system are manifested. As a result several inflammatory mediators are up regulated through multiple mechanisms. The up regulation of inflammatory mediators such as anaphylatoxin C5a (C5a), procalcitonin (PCT), interleukin 6 (IL-6), interleukin 10 (IL-10), myeloperoxidase (MPO), C reactive protein (CRP), and circulating levels of hemostatic markers including protein C inhibitor (PCI), plasminogen activator inhibitor 1 (PAI-1), and protein C (Pr C) were evaluated in 758 subjects enrolled in a randomized, double-blind, placebo-controlled, Phase-2B study evaluating the safety and efficacy of recombinant thrombomodulin (ART-123) in subjects with sepsis and suspected DIC. Thirty healthy male and female volunteers served as the control group. Commercially available ELISA methods were used to measure the various mediators. Marked deviations in the circulating levels of these markers, as compared to controls, were noted as shown in the following table. Compared with controls, subjects in DIC showed an increase in the circulating levels of most inflammatory markers. The levels of PCT, IL-6 and CRP, where considerably higher in the DIC subjects whereas PCI, Pr C and AT exhibited slight decreases. Wide individual variations were present. The PAI-1 levels were also increased in the DIC subjects. These results are tabulated below. These results clearly indicate that inflammation and impairment of fibrinolysis play a key role in the pathogenesis of DIC Parameter Nomal (NHP Mean+SEM) DIC (Baseline Mean+SEM) % Change Protein C (% Ag) 82.5 ± 13.6 47.6 ± 23.7 −42.2% Functional Protein C (%) 83.4 ± 13.2 46.2 ± 29.8 −44.6% PCI (% Inhibition) 130.0 ± 24.6 79.4 ± 105.5 −38.9% PAI-1 (ng/ml) 35.4 ± 10.8 140.6 ± 165.6 297.1% CRP (ug/ml) 2.6 ± 0.4 48.0 ± 14.2 1736.9% C5a (ng/ml) 9.2 ± 3.2 17.2 ± 13.3 85.1% IL-6 (pg/ml) 9.3 ± 3.7 620.3 ± 1883.4 6583.9% IL-10 (pg/ml) 13.9 ± 13.1 130.2 ± 118.6 836.1% MPO (ng/ml) 16.0 ± 4.2 108.1 ± 68.6 574.6% PCT (ng/ml) 0.2 ± 0.13 21.9 ± 43.3 14514.5% Disclosures: Osawa: Asahi Kasei Pharma America Corporation: Employment. Kaul:Asahi Kasei Pharma America Corporation: Employment.

scholarly journals Prognostic Factors in Patients with Septic Disseminated Intravascular Coagulation Treated with Thrombomodulin: The Effect of Reduced Thrombomodulin Dose; a Single-center, Retrospective, Observational Study

2021 ◽  
Author(s):  
Yoshihiro Nishita ◽  
Masatoshi Taga ◽  
Masaru Sakurai ◽  
Yoshitsugu Iinuma ◽  
Togen Masauji
Keyword(s):  
Prognostic Factors ◽  
Side Effects ◽  
Renal Dysfunction ◽  
Dose Reduction ◽  
Disseminated Intravascular Coagulation ◽  
Sofa Score ◽  
Single Center ◽  
Intravascular Coagulation ◽  
Reduced Dose ◽  
All Cause Mortality

Abstract Background: Human soluble recombinant thrombomodulin (TM alfa), a treatment for septic Disseminated intravascular coagulation (DIC), is recommended for patients with severe renal dysfunction in reduced doses. However, no studies have examined yet how dose reduction affects clinical efficacy. In this study, we investigated the significance of the TM alfa dose as a prognostic factor in clarifying the clinical background factors related to the clinical effect of TM alfa in patients with septic DIC.Methods: This study involved 102 patients with septic DIC admitted to a single-center intensive care unit between April 2013 and March 2020, receiving TM alfa. The following factors were retrospectively collected from the medical records of the target patients: (1) patient background, (2) sequential organ failure assessment (SOFA) score, (3) Japanese Association for Acute Medicine DIC diagnostic criteria score, (4) DIC treatment information, (5) TM alfa dose per bodyweight (normal dose: 0.06 mg/kg or reduced dose: 0.02 mg/kg), (6) DIC resolution within 7 days after the start of TM alfa administration (DIC resolution), (7) all deaths within 30 days after the start of TM alfa administration (30-days-all-cause mortality), (8) presence or absence of new hemorrhagic side effects after the start of TM alfa administration. Multiple logistic regression analysis was used to assess factors associated with DIC resolution and 30-days-all-cause mortality.Results: The SOFA score (odds ratio: 95% confidence interval, 0.76: 0.66–0.89), pneumonia (0.24: 0.08–0.75), and reduced dose administration of TM alfa (0.23: 0.08–0.66) were independent of and negatively related to the DIC resolution. For the 30-days-all-cause mortality, the SOFA score (1.66: 1.31–2.09), pneumonia (9.50: 2.49–36.25), and TM alfa dose reduction (3.52: 1.06–11.69) were independent, poor prognostic factors. We found no association between the hemorrhagic side effects and the TM alfa dose per bodyweight.Conclusions: The reduced dose of TM alfa for patients with severe renal dysfunction was observed to be an influential factor for DIC resolution and 30-day all-cause mortality in addition to SOFA score and pneumonia. Further studies are required in the future to verify this finding.

Dysregulation of Inflammatory and Hemostatic Markers In Disseminated Intravascular Coagulation.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3656-3656
Author(s):  
Debra Hoppensteadt ◽  
Josephine Cunanan ◽  
Nasiredin Sadeghi ◽  
Inder Kaul ◽  
Jawed Fareed
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Inflammatory Mediators ◽  
Protein C ◽  
Control Group ◽  
Normal Male ◽  
Plasminogen Activator Inhibitor 1 ◽  
Intravascular Coagulation ◽  
Hemostatic Markers ◽  
Circulating Levels ◽  
Pai 1

Abstract Abstract 3656 Disseminated intravascular coagulation (DIC) represents a complex polypathologic syndrome where marked alterations in the hemostatic system are manifested. As a result several inflammatory mediators are upregulated through multiple mechanisms. The upregulation of inflammatory mediators such as anaphylatoxin C5a (C5a), procalcitonin (PCT), interleukin 6 (IL-6), interleukin 10 (IL-10), myeloperoxidase (MPO) and c reactive protein (CRP), and circulating levels of hemostatic markers including protein C inhibitor (PCI), plasminogen activator inhibitor 1 (PAI-1), prothrombin fragment1.2 (F1.2), thrombin antithrombin complex (TAT), antithrombin (AT), activated protein C (APC) and protein C (Pr C) were evaluated in the baseline samples of an initial cohort of provisionally diagnosed DIC and sepsis patients enrolled in an ongoing clinical trial designed to assess the safety and efficacy of r-thrombomodulin (ART-123) (n=100). The control group consisted of normal male and female volunteers (n=30). Commercially available ELISA methods were used to measure the various mediators. Marked deviations in the circulating levels of these markers, as compared to controls, were noted as shown in the following table. Compared with normal volunteers, patients showed a 5–10 fold increase in the circulating level of most inflammatory markers, with the exception of PCT, IL-6 and CRP, where the increase was over 50 fold. PCI, Pr C and AT exhibited slight decreases. Wide individual variations were obvious. These results clearly indicate that inflammation, thrombin generation, impairment of fibrinolysis and impairment of endogenous anticoagulants play a key role in the pathogenesis of DIC. Marker Normal Human Volunteers (n=30) DIC with Sepsis Patients (n=100) Fold Change PCT (ng/ml) 0.1 ± 0.04 (0.01) 18.7 ± 31.2 (3.1) 187× Increase C5a (ng/ml) 6.7 ± 1.7 (0.5) 15.5.7 ± 14.9 (1.5) 2× Increase PCI (% NHP) 138.9 ± 71.1 (8.8) 106.9 ± 33.4 (7.1) 1.3× Decrease IL-6 (pg/ml) 2.5 ± 1.2 (0.3) 522.5 ± 881.5 (88.2) 210× Increase IL-10 (pg/ml) 9.8 ± 5.23 (1.7) 46.9 ± 73.3 (8.8) 5× Increase MPO (ng/ml) 15.1 ± 10.1 (2.7) 111.4 ± 74.9 (7.5) 7× Increase PAI-1 (ng/ml) 31.7 ± 8.9 (3.1) 130.2 ± 178.1 (22.1) 4× Increase F1.2 (pM) 108.6 ± 46.2 (12.3) 473.7 ± 320.2 (32.0) 4× Increase TAT (ng/ml) 4.4 ± 1.1 (0.3) 17.0 ± 30.8 (3.1) 5× Increase AT (% NHP) 94.2 ± 10.3 (2.7) 80.4 ± 30.7 (3.1) 1.2× Decrease APC (ratio) 2.23 ± 0.3 (0.1) 2.48 ± 0.4 (0.04) 1.1× Increase CRP (ug/ml) 0.5 ± 1.1 (0.3) 38.4 ± 3.9 (0.4) 76× Increase Pr. C (% NHP) 78.3 ± 13.3 (3.6) 41.3 ± 17.4 (1.7) 2× Decrease Disclosures: Kaul: Artisan Pharma: Employment.

scholarly journals Clinical phenotypes from fatal cases of acute respiratory distress syndrome caused by pneumonia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kazuya Ichikado ◽  
Kodai Kawamura ◽  
Takeshi Johkoh ◽  
Kiminori Fujimoto ◽  
Ayumi Shintani ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Prognostic Factors ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Disseminated Intravascular Coagulation ◽  
Distress Syndrome ◽  
Fatal Outcome ◽  
Apache Ii ◽  
Apache Ii Score ◽  
Intravascular Coagulation

AbstractThere have been no report of objective clinical characteristics or prognostic factors that predict fatal outcome of acute respiratory distress syndrome (ARDS) since the Berlin definition was published. The aim of this study is to identify clinically available predictors that distinguish between two phenotypes of fatal ARDS due to pneumonia. In total, 104 cases of Japanese patients with pneumonia-induced ARDS were extracted from our prospectively collected database. Fatal cases were divided into early (< 7 days after diagnosis) and late (≥ 7 days) death groups, and clinical variables and prognostic factors were statistically evaluated. Of the 50 patients who died within 180 days, 18 (36%) and 32 (64%) were in the early (median 2 days, IQR [1, 5]) and late (median 16 days, IQR [13, 29]) death groups, respectively. According to multivariate regression analyses, the APACHE II score (HR 1.25, 95%CI 1.12–1.39, p < 0.001) and the disseminated intravascular coagulation score (HR 1.54, 95%CI 1.15–2.04, p = 0.003) were independent prognostic factors for early death. In contrast, late death was associated with high-resolution computed tomography (HRCT) score indicating early fibroproliferation (HR 1.28, 95%CI 1.13–1.42, p < 0.001) as well as the disseminated intravascular coagulation score (HR 1.24, 95%CI 1.01–1.52, p = 0.039). The extent of fibroproliferation on HRCT, and the APACHE II scores along with coagulation abnormalities, should be considered for use in predictive enrichment and personalized medicine for patients with ARDS due to pneumonia.

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