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.

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 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 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 Antithrombin use and mortality in patients with stage IV solid tumor-associated disseminated intravascular coagulation: a nationwide observational study in Japan

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Kohei Taniguchi ◽  
Hiroyuki Ohbe ◽  
Kazuma Yamakawa ◽  
Hiroki Matsui ◽  
Kiyohide Fushimi ◽  
...  
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Solid Tumor ◽  
Stage Iv ◽  
Therapeutic Strategies ◽  
Control Group ◽  
Intravascular Coagulation ◽  
High Care ◽  
Nationwide Observational Study ◽  
General Wards ◽  
Inpatient Database

Abstract Background Terminal-stage solid tumors are one of the main causes of disseminated intravascular coagulation (DIC); effective therapeutic strategies are therefore warranted. This study aimed to investigate the association between mortality and antithrombin therapy in patients with stage IV solid tumor-associated DIC using a large nationwide inpatient database. Methods From July 2010 to March 2018, patients with stage IV solid tumor-associated DIC in the general wards, intensive care unit, or high care unit were identified using the Japanese Diagnosis Procedure Combination Inpatient Database. Patients who received antithrombin within 3 days of admission were allocated to the antithrombin group, while the remaining patients were allocated to the control group. One-to-four propensity score matching analyses were applied to compare outcomes. The primary outcome was the 28-day in-hospital mortality. Results Of the 25,299 eligible patients, 919 patients had received antithrombin within 3 days of admission and were matched with 3676 patients in the control group. There were no significant differences in the 28-day mortality between the two groups (control vs. antithrombin: 28.9% vs. 30.3%; hazard ratio, 1.08; 95% confidence interval, 0.95–1.23). There were no significant differences in the organ failure score and the proportion of critical bleeding between the two groups. Subgroup analyses showed that the effects of antithrombin were not significantly different among different tumor types. Conclusion Using a nationwide Japanese inpatient database, this study showed that there is no association between antithrombin administration and 28-day mortality in patients with stage IV solid tumor-associated DIC. Therefore, establishing other therapeutic strategies for solid tumor-associated DIC is required.

Increasing concentrations of prothrombin complex concentrate induce disseminated intravascular coagulation in a pig model of coagulopathy with blunt liver injury

Blood ◽  
2011 ◽  
Vol 118 (7) ◽  
pp. 1943-1951 ◽  
Author(s):  
Oliver Grottke ◽  
Till Braunschweig ◽  
Henri M. H. Spronk ◽  
Stephanie Esch ◽  
Annette D. Rieg ◽  
...  
Keyword(s):  
Liver Injury ◽  
Blood Loss ◽  
Disseminated Intravascular Coagulation ◽  
Prothrombin Complex Concentrate ◽  
Safety Data ◽  
Control Group ◽  
Total Blood ◽  
Intravascular Coagulation ◽  
Blunt Liver Injury ◽  
Ringer’S Lactate

Abstract Despite increasing use of prothrombin complex concentrate (PCC) to treat hemorrhage-associated coagulopathy, few studies have investigated PCC in trauma, and there is a particular lack of safety data. This study was performed to evaluate PCC therapy in a porcine model of coagulopathy with blunt liver injury. Coagulopathy was induced in 27 anesthetized pigs by replacing approximately 70% blood volume with hydroxyethyl starch 130/0.4 and Ringer's lactate solution; erythrocytes were collected and retransfused. Ten minutes after trauma, animals randomly received PCC (35 or 50 IU/kg) or saline. Coagulation parameters including thromboelastometry, thrombin generation, and blood loss were monitored for 2 hours. Internal organs were examined macroscopically and histologically to determine the presence of emboli and assess liver injury. Total blood loss was significantly lower and survival was higher in both PCC groups versus the control group (P < .05). These outcomes appeared to be dose-independent. Thromboembolism was found in all animals treated with 50 IU/kg PCC; 44% also showed signs of disseminated intravascular coagulation. Liver injury was similar in all animals. In conclusion, 35 IU/kg PCC safely improved coagulation and attenuated blood loss. However, the higher dose of PCC (50 IU/kg) appeared to increase the risk of thromboembolism and disseminated intravascular coagulation.

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