scholarly journals Clinical Investigation of Coagulation Markers for Early Detection of Sepsis-Induced Disseminated Intravascular Coagulation: A Single-Center, Prospective Observational Study

2018 ◽  
Vol 24 (7) ◽  
pp. 1082-1087 ◽  
Author(s):  
Takamitsu Masuda ◽  
Tomohisa Shoko ◽  
Yoshizumi Deguchi
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Clinical Investigation ◽  
Plasminogen Activator Inhibitor ◽  
Rank Test ◽  
Acute Medicine ◽  
Soluble Fibrin ◽  
Intravascular Coagulation ◽  
Cutoff Values ◽  
Failure Assessment ◽  
Pai 1

Disseminated intravascular coagulation (DIC) often complicates sepsis, and its early treatment is crucial for improving patient outcomes. Coagulation markers may enable earlier diagnosis of DIC. The purpose of this study was to evaluate whether the risk of DIC onset can be predicted using coagulation markers. Patients who showed symptoms of systemic inflammatory response syndrome ≥2 and the quick Sequential Organ Failure Assessment score ≥2 points were investigated. All blood samples collected from the time of hospital admission to 7 days postadmission were investigated. Patients were classified according to time of DIC onset (1) no DIC group (not DIC developed), (2) pre-DIC group (DIC onset >24 hours after admission), (3) DIC group (DIC onset at time of the admission) and according to cutoff values of coagulation markers, High group and Low group. Statistical differences were analyzed by log-rank test, Kruskal-Wallis rank test, and Friedman test. A total of 107 patients were enrolled in the study. Soluble fibrin (SF), plasminogen activator inhibitor (PAI)-1, and d-dimer levels were significantly increased even under pre-DIC conditions. Japanese Association for Acute Medicine (JAAM) DIC scores increased significantly over time in the High SF group (≥31.0 µg/mL) and High PAI-1 group (≥49.0 ng/mL), while JAAM DIC scores in the Low SF group remained ≤3 until day 7. We proposed the cutoff values of SF as 31 µg/mL to detect early phase of DIC. Soluble fibrin might be useful not only to predict DIC but also to exclude a diagnosis of DIC.

Clinical course and outcome of disseminated intravascular coagulation diagnosed by Japanese Association for Acute Medicine criteria

2008 ◽  
Vol 100 (12) ◽  
pp. 1099-1105 ◽  
Author(s):  
Satoshi Gando ◽  
Daizoh Saitoh ◽  
Hiroshi Ogura ◽  
Toshihiko Mayumi ◽  
Kazuhide Koseki ◽  
...  
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Clinical Course ◽  
Trauma Patients ◽  
Acute Medicine ◽  
Japanese Association ◽  
Intravascular Coagulation ◽  
Coagulation Abnormalities ◽  
Failure Assessment ◽  
Jaam Criteria ◽  
Prothrombin Time Ratio

SummaryThe Japanese Association for Acute Medicine (JAAM) disseminated intravascular coagulation (DIC) study group recently announced new diagnostic criteria for DIC. These criteria have been prospectively validated and demonstrated to progress to overt DIC as defined by the International Society on Thrombosis and Haemostasis (ISTH).Although an underlying condition is essential for the development of DIC, it has never been clarified if patients with different underlying disorders have a similar course. Among 329 patients with DIC diagnosed by the JAAM criteria, those with underlying sepsis (n=98) or trauma (n=95) were compared. The 28-day mortality rate was significantly higher in sepsis patients than trauma patients (34.7% vs. 10.5%, p<0.0001).Within three days of fulfilling the JAAM criteria, sepsis patients had a lower platelet count, higher prothrombin time ratio, higher systemic inflammatory response syndrome score, and higher Sequential Organ Failure Assessment score compared with trauma patients. On day 3, a significantly higher percentage of trauma patients than sepsis patients showed improvement of DIC (64.2% vs. 30.6%, p<0.001).These differences were mainly due to patients with lower JAAM DIC scores. More than 50% of the JAAM DIC patients with sepsis who died within 28 days could not be detected by ISTH DIC criteria during the initial three days. In contrast, most trauma patients who died within 28 days had DIC simultaneously diagnosed by JAAM and ISTH criteria, except for those with brain death. These findings suggest that coagulation abnormalities, organ dysfunction, and the outcome of JAAM DIC differ between patients with sepsis and trauma.

scholarly journals The specific activity of plasminogen activator inhibitor-1 in disseminated intravascular coagulation with acute promyelocytic leukemia

Blood ◽  
1991 ◽  
Vol 77 (9) ◽  
pp. 1949-1957 ◽  
Author(s):  
Y Sakata ◽  
T Murakami ◽  
A Noro ◽  
K Mori ◽  
M Matsuda
Keyword(s):  
Plasminogen Activator ◽  
Acute Promyelocytic Leukemia ◽  
Disseminated Intravascular Coagulation ◽  
Specific Activity ◽  
Plasminogen Activator Inhibitor ◽  
Promyelocytic Leukemia ◽  
Plasminogen Activator Inhibitor 1 ◽  
Intravascular Coagulation ◽  
Activator Inhibitor ◽  
Pai 1

In disseminated intravascular coagulation (DIC) with acute promyelocytic leukemia (APL) in the absence of severe infection, marked fibrinolysis was noted in comparison with normal levels of antithrombin III, which is a major inhibitor of the coagulation system. Increased plasminogen activator inhibitor-1 (PAI-1) antigen levels in plasma from patients with septicemia decreased the ratio of the plasma clot lysis rate induced by an anti-alpha 2-plasmin inhibitor monoclonal antibody to the tissue-type plasminogen activator (t-PA) concentration. This decrease was not as prominent in plasma from patients with DIC, especially those with APL. To explore the character of PAI-1 in these plasmas, we measured the specific activity of PAI-1 by determining the ratio of active PAI-1 antigen to t-PA-unbound PAI-1 antigen. To calculate the amount of active PAI-1 antigen, the amount of t-PA/PAI-1 complex before and after the addition of a fixed amount of t-PA to the sample was measured by a sandwich solid-phase enzyme-linked immunosorbent assay using anti-PAI-1 and anti-t-PA monoclonal antibodies. The assay to measure total PAI-1 antigen used three monoclonal anti-PAI-1 antibodies and had similar sensitivities to free active, latent, vitronectin-bound and t-PA-bound PAI-1. The specific activity of PAI-1 decreased in patients with DIC (43.7% +/- 30.6%) and in DIC cases with APL (10.3% +/- 6.0%) in comparison to patients with septicemia (83.7% +/- 20.2%) or normal controls (85.8% +/- 27.3%). In DIC associated with APL, degraded forms of PAI-1 were detected in plasma by immunoblotting. These results suggest that a decrease in the specific activity of PAI-1 and an increase in secondary fibrinolysis result in a hyperfibrinolytic state in DIC patients with APL.

scholarly journals Usefulness of Measuring Changes in SOFA Score for the Prediction of 28-Day Mortality in Patients With Sepsis-Associated Disseminated Intravascular Coagulation

2019 ◽  
Vol 25 ◽  
pp. 107602961882404 ◽  
Author(s):  
Toshiaki Iba ◽  
Makoto Arakawa ◽  
Katsunori Mochizuki ◽  
Osamu Nishida ◽  
Hideo Wada ◽  
...  
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Sofa Score ◽  
Operating Characteristic ◽  
Japanese Society ◽  
Characteristic Curve ◽  
Curve Analysis ◽  
Acute Medicine ◽  
Intravascular Coagulation ◽  
Failure Assessment ◽  
Sepsis Trial

The primary end point for sepsis trial is 28-day mortality. However, additional methods for determining the efficacy may have benefits. The purpose of this study was to search a useful indicator of anticoagulant therapy in patients with sepsis with disseminated intravascular coagulation (DIC). Data from 323 patients with sepsis with coagulopathy treated with antithrombin supplementation were analyzed. The changes in the Sequential Organ Failure Assessment (Δ SOFA) score, the overt-DIC (Δ overt-DIC) score, and the Japanese Society for Acute Medicine DIC (Δ JAAM DIC) score from baseline to day 7 were retrospectively analyzed in relation to the 28-day mortality. Significant correlations were found between the 28-day mortality and Δ SOFA, Δ overt-DIC score, and Δ JAAM DIC score. The accuracy of the prediction was higher for Δ SOFA (80.5%) than for Δ overt-DIC (66.7%, P < .001). The areas under the curve for mortality calculated using a receiver operating characteristic curve analysis were 0.812 for Δ SOFA, 0.655 for Δ overt-DIC, and 0.693 for Δ JAAM DIC. The mortality rate was significantly lower among cases with an improved SOFA score compared to those without an improvement. The Δ SOFA had the strongest association with the 28-day mortality in patients with sepsis and DIC.

scholarly journals The specific activity of plasminogen activator inhibitor-1 in disseminated intravascular coagulation with acute promyelocytic leukemia

Blood ◽  
1991 ◽  
Vol 77 (9) ◽  
pp. 1949-1957 ◽  
Author(s):  
Y Sakata ◽  
T Murakami ◽  
A Noro ◽  
K Mori ◽  
M Matsuda
Keyword(s):  
Plasminogen Activator ◽  
Acute Promyelocytic Leukemia ◽  
Disseminated Intravascular Coagulation ◽  
Specific Activity ◽  
Plasminogen Activator Inhibitor ◽  
Promyelocytic Leukemia ◽  
Plasminogen Activator Inhibitor 1 ◽  
Intravascular Coagulation ◽  
Activator Inhibitor ◽  
Pai 1

Abstract In disseminated intravascular coagulation (DIC) with acute promyelocytic leukemia (APL) in the absence of severe infection, marked fibrinolysis was noted in comparison with normal levels of antithrombin III, which is a major inhibitor of the coagulation system. Increased plasminogen activator inhibitor-1 (PAI-1) antigen levels in plasma from patients with septicemia decreased the ratio of the plasma clot lysis rate induced by an anti-alpha 2-plasmin inhibitor monoclonal antibody to the tissue-type plasminogen activator (t-PA) concentration. This decrease was not as prominent in plasma from patients with DIC, especially those with APL. To explore the character of PAI-1 in these plasmas, we measured the specific activity of PAI-1 by determining the ratio of active PAI-1 antigen to t-PA-unbound PAI-1 antigen. To calculate the amount of active PAI-1 antigen, the amount of t-PA/PAI-1 complex before and after the addition of a fixed amount of t-PA to the sample was measured by a sandwich solid-phase enzyme-linked immunosorbent assay using anti-PAI-1 and anti-t-PA monoclonal antibodies. The assay to measure total PAI-1 antigen used three monoclonal anti-PAI-1 antibodies and had similar sensitivities to free active, latent, vitronectin-bound and t-PA-bound PAI-1. The specific activity of PAI-1 decreased in patients with DIC (43.7% +/- 30.6%) and in DIC cases with APL (10.3% +/- 6.0%) in comparison to patients with septicemia (83.7% +/- 20.2%) or normal controls (85.8% +/- 27.3%). In DIC associated with APL, degraded forms of PAI-1 were detected in plasma by immunoblotting. These results suggest that a decrease in the specific activity of PAI-1 and an increase in secondary fibrinolysis result in a hyperfibrinolytic state in DIC patients with APL.

scholarly journals Plasma Levels of Total Plasminogen Activator Inhibitor-I (PAI-I) and tPA/PAI-1 Complex in Patients With Disseminated Intravascular Coagulation and Thrombotic Thrombocytopenic Purpura

2001 ◽  
Vol 7 (3) ◽  
pp. 229-233 ◽  
Author(s):  
Rika Watanabe ◽  
Hideo Wada ◽  
Youichi Miura ◽  
Youichi Murata ◽  
Yasuyuki Watanabe ◽  
...  
Keyword(s):  
Organ Failure ◽  
Plasminogen Activator ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Disseminated Intravascular Coagulation ◽  
Plasma Levels ◽  
Plasminogen Activator Inhibitor ◽  
Thrombocytopenic Purpura ◽  
Intravascular Coagulation ◽  
Activator Inhibitor ◽  
Pai 1

In this study, we examined changes in the plasma levels of total plasminogen activator inhibitor-I (PAI-I) and tissue-type plasminogen activator (tPA)/PAI-I complex in patients with disseminated intravascular coagulation (DIC) and in those with thrombotic thrombocytopenic purpura (TTP) to investigate the fibrinolytic function and its relation to organ failure, The plasma levels of total PAI-I and tPA/PAI-I complex were significantly higher in patients with DIC, pre-DIC, and TTP than in those with non-DIC. The plasma levels of thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC), D-dimer, thrombomodulin (TM), total PAI-I, and tPA/PAI-I complex were significantly higher in patients with organ failure than in those without organ failure. The plasma levels of total PAI-I and tPA/PAI-I complex were markedly increased in patients with acute leukemia. The plasma levels of total PAI-1, but not those of tPA/PAI-I complex, were significantly increased in patients with sepsis or with solid cancer. In all cases, total PAI-I or tPA/PAI-I complex was not significantly correlated with any hemostatic marker. Measurement of total PAI-I and tPA/PAI-I complex may be useful in the diagnosis of DIC.

scholarly journals Simvastatin improves the prognosis of endotoxin-induced disseminated intravascular coagulation by regulating the intestinal microenvironment

2020 ◽  
Author(s):  
Min Xu ◽  
Lili Luo ◽  
Mengyi Du ◽  
Lu Tang ◽  
Jie Zhou ◽  
...  
Keyword(s):  
Bacterial Translocation ◽  
Disseminated Intravascular Coagulation ◽  
Intestinal Barrier ◽  
Plasminogen Activator Inhibitor ◽  
Coagulation Factors ◽  
Organ Damage ◽  
Multiple Organ ◽  
Plasminogen Activator Inhibitor 1 ◽  
Intravascular Coagulation ◽  
Coagulation Dysfunction

Abstract Background: Disseminated intravascular coagulation (DIC) is characterized by extensive endothelial injury and coagulation activation that is primarily caused by infection and can be aggravated by the gut due to increased permeability and bacterial translocation. Studies have shown that statins play an important role in reducing inflammation, protecting the endothelium and improving coagulation. In addition, statins regulate tight junction (TJ) proteins and gut microbes. Therefore, we aimed to investigate whether simvastatin improves DIC prognosis by regulating the intestinal microenvironment. Methods: Mice were administered 20 mg/kg simvastatin by gavage for 2 weeks and then intraperitoneally injected with 50 mg/kg endotoxin. Twelve hours later, cytokine release, coagulation dysfunction, multiple organ damage and survival were assessed. In addition, intestinal barrier and permeability and bacteria and bacteria translocation were evaluated. Results: We found that the severity of endotoxin-induced DIC was significantly improved in simvastatin-pretreated mice, who showed attenuated depletion of coagulation factors and platelets, decreased plasminogen activator inhibitor-1 (PAI-1) expression, reduced organ fibrin deposition and an improved survival rate. In addition, simvastatin reduced epithelial apoptosis, increased TJ gene expression, and upregulated antimicrobial peptides, lysozyme and mucins. Simvastatin-pretreated mice showed increased Lactobacillales counts, while the LPS group had increased numbers of Desulfovibrio and Mucispirillum, which produce harmful toxins and damage the intestinal epithelium and mucosa. Finally, with the decreased intestinal permeability in the simvastatin group, bacterial translocation in the organs and blood was significantly reduced, both in quantity and species. Conclusions: Simvastatin improves DIC prognosis, and the intestinal microenvironment participates in this process.

scholarly journals Impact of Antithrombin Supplementation and Concomitant Anticoagulation Therapy in Pediatric Patients With Disseminated Intravascular Coagulation

2019 ◽  
Vol 25 ◽  
pp. 107602961983435
Author(s):  
Hiroyuki Nagafuchi ◽  
Yutaka Eguchi ◽  
Toshiaki Ikeda
Keyword(s):  
Organ Failure ◽  
Disseminated Intravascular Coagulation ◽  
Pediatric Patients ◽  
Anticoagulation Therapy ◽  
Standardized Mortality Ratio ◽  
Efficacy And Safety ◽  
Resolution Rate ◽  
Intravascular Coagulation ◽  
Failure Assessment ◽  
Mortality Ratio

We aimed to evaluate the efficacy and safety of antithrombin (AT) supplementation and concomitant anticoagulation therapy in 65 children who met the Japanese Ministry of Health and Welfare (JMHW) disseminated intravascular coagulation (DIC) criteria and had received AT concentrate and/or other concomitant anticoagulants. The primary efficacy end point was to determine standardized mortality ratio (SMR). The secondary efficacy end points were DIC resolution rate and pediatric sequential organ failure assessment (pSOFA) score on day 3. The 28-day mortality rate was 6.8%; SMR was 0.55. Disseminated intravascular coagulation resolution rate on day 3 was 54.5%. The JMHW DIC scores at day 0 ( P = .005) and pSOFA scores at day 3 ( P = .018) were significantly lower in patients with resolution of DIC than in those without resolution of DIC. The target cutoff value for JMHW DIC score on day 0 was 6. No bleeding-related adverse events were associated with AT administration. In children with DIC, AT supplementation and concomitant anticoagulation therapy can be safely used as initial treatment when JMHW DIC score is 6; it may improve DIC resolution, organ failure, and mortality rates.

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.

Disseminated intravascular coagulation secondary to advanced prostate cancer: Clinical characteristics, management, and prognosis.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 355-355
Author(s):  
Benny Ni ◽  
Jue Wang
Keyword(s):  
Prostate Cancer ◽  
Cancer Therapy ◽  
Clinical Features ◽  
Disseminated Intravascular Coagulation ◽  
Single Case ◽  
Therapy Group ◽  
Rank Test ◽  
Entire Cohort ◽  
Intravascular Coagulation ◽  
Presenting Symptoms

355 Background: Although disseminated intravascular coagulation (DIC) is a recognized complication of prostate cancer, little is known about the clinical features and optimal management of these patients. Although anecdotal case studies indicating that the prognosis of prostate cancer associated with DIC might improve with chemotherapy, the clinical data from single case report are far from sufficient for establishment of a standardized treatment strategy. The main objective of this study was to determine the clinical features, treatment and prognosis clinical outcome of patients with prostate cancer complicated by DIC. Methods: We conducted a pooled analysis of 85 prostate cancer patients diagnosed with DIC, two treated in our institution and 83 patients from published literature between January 1976 and June 2017. Results: Eighty-five patients were included in final analysis. The median age was 68 years (range, 44 to 92 years). The majority of patients (98%) has adenocarcinoma. Two (2%) patients with small cell carcinoma. The median of PSA was 614 ng/ml (range: 0.8 – 8138). A Gleason score of 8 or higher was found in 67% of patients. Distant metastasis was reported in 98% of patients. At diagnosis of DIC, the median platelet count was 75 *109 /L (range: 3-205). Regarding the presenting symptoms of DIC, subcutaneous bleeding was reported in 64% of cases; hematuria in 27%. Invasive procedure including prostate biopsy might have been the provoking events of DIC in 25% of the cases. Seventy-one patients received cancer directed therapy including various androgen deprivation, chemotherapy, and novel androgen signaling inhibitor, whereas 13 patients received only best supportive care (BSC). The median overall survival (OS) of the entire cohort of patients was 10 months (95% confidence interval [CI], 5.3-14.7). Significantly prolonged OS was observed in the cancer therapy group, with a median survival of 12 months compared to 2 weeks in the BSC group (p < 0.001, log-rank test). Conclusions: Our analysis showed that patients with prostate cancer complicated by DIC had very poor prognosis, and active cancer therapy might improve OS of these patients.

Sign in / Sign up

Export Citation Format

Share Document