Limited Superiority Of Recombinant Thrombomodulin For Disseminated Intravascular Coagulation; A Comparative Analysis In 41 Children

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3614-3614
Author(s):  
Eri Nishikawa ◽  
Hiroshi Yagasaki ◽  
Katsuyoshi Shimozawa ◽  
Hirotsugu Okuma ◽  
Maiko Hirai ◽  
...  
Keyword(s):  
Overall Survival ◽  
Disseminated Intravascular Coagulation ◽  
Cumulative Incidence ◽  
Platelet Transfusion ◽  
Conventional Treatment ◽  
Conflicts Of Interest ◽  
Control Group ◽  
Limited Information ◽  
Intravascular Coagulation ◽  
Recombinant Thrombomodulin

Abstract Background and Objectives Recombinant thrombomodulin (rTM), a new type of natural anticoagulant, has been available in Japan since 2008 for the treatment of disseminated intravascular coagulation (DIC). Since limited information is available on its efficacy in children, we compared the efficacy of rTM to that of conventional treatment. Patients and Methods Of 41 children with DIC, 21 were treated with rTM as a first-line therapy (rTM group) and 20 weere treated with conventional treatment (control group). The day on which anti-DIC treatment was first given was defined as day 1. We used the DIC criteria of the Japan Welfare and Health Ministry. We evaluated the overall survival at day 28 after anti-DIC treatment, the cumulative incidence of DIC resolution, and the total fresh frozen plasma (FFP) and platelet transfusion volumes during the course of DIC. Results Clinical outcomes are summarized in the Table. Both groups showed comparable overall survival (95.2% in the rTM group and 95.0% in the control group). In addition, the cumulative incidence of DIC resolution in the rTM group (90.5%) was not different from that in the control group (70.0%) (p=0.210) (Figure). However, the median FFP and platelet transfusion volumes in the rTM group (0 U/kg and 0.28 U/kg) were lower those in the control group (0.14 U/kg and 0.76 U/kg) (p=0.041 and 0.063, respectively). Conclusion The use of rTM in children with DIC should reduce the social and ethical problems as well as the biological risks associated with human-derived blood products. Although the limited advantages of rTM were shown, the present study was limited by the small and heterogeneous patient population. Therefore, larger prospective studies are warranted to fully evaluate the efficacy of rTM. Disclosures: No relevant conflicts of interest to declare.

Soluble Recombinant Thrombomodulin Is a Potentially Promising Agent without Causing Severe Hemorrhagic Events for Hematological Malignancy-Induced Disseminated Intravascular Coagulation

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3413-3413
Author(s):  
Naoki Kurita ◽  
Hidekazu Nishikii ◽  
Yasuhisa Yokoyama ◽  
Mamiko Sakata-Yanagimoto ◽  
Naoshi Obara ◽  
...  
Keyword(s):  
Overall Survival ◽  
Disseminated Intravascular Coagulation ◽  
Hematological Malignancies ◽  
Hematological Malignancy ◽  
Phase Iii ◽  
Bleeding Tendency ◽  
Phase Iii Trial ◽  
Intravascular Coagulation ◽  
Hemorrhagic Events ◽  
Recombinant Thrombomodulin

Abstract Abstract 3413 Background: Disseminated intravascular coagulation (DIC) is a lethal complication in patients with hematological malignancies. Although standard therapy against DIC remains to be established, soluble recombinant thrombomodulin (rTM), which serves as a receptor for thrombin, has been developed and its effectiveness for DIC was recently reported (Saito et al, J Thromb Haemost 2006). We retrospectively analyzed 55 DIC episodes treated with rTM in patients with hematological malignancies. Patients and Methods: 55 consecutive DIC episodes in 47 patients with hematological malignancies (AML except for APL, 21; APL, 8; ALL, 8; lymphoma, 8; myeloma, 2) hospitalized between November 2009 and July 2012 in University of Tsukuba Hospital were retrospectively analyzed. Diagnosis of DIC was based on DIC score of Japanese Ministry of Health and Labor Welfare criteria (Kobayashi et al, Bibl Haematol 1983). DIC was induced by hematological malignancy itself and severe infection secondary to hematological malignancy in 39 and 16 episodes, respectively. In every episode, 380 units/kg/day of rTM was administered intravenously from the onset of DIC for median of 7 (range, 2–22) days. The fibrin degradation products (FDP) level, DIC score, recovery time from DIC (recovery, the day when DIC score was decreased to 5 or less), and overall survival were analyzed. Results: Median DIC score at the onset was 7 (range, 6–11). 15 episodes were accompanied by bleeding tendency. Average of FDP level at the onset was 64.6 ƒÊg/dl (range, 20.6–202.4) in malignancy-induced DIC and 30.1 ƒÊg/dl (range, 13.2–72.0) in infection-induced DIC (P=0.03). FDP level 14 days after rTM administration was 10.1 ƒÊg/dl (SD: 3.7–27.9) and 20.3 ƒÊg/dl (SD: 9.3–44.3), respectively (P=0.04). Recovery rates from DIC 7 days after rTM administration were 72% in malignancy-induced DIC and 39% in infection-induced DIC (Fig. 1, P=0.02), and 100-day overall survival after the onset of DIC were 89% and 15% (Fig. 2, P<0.01), respectively. In multivariate analysis, infection-induced DIC was an only significant risk factor and presence of bleeding tendency, FDP level at the onset, DIC score at the onset, period of rTM administration, and number of rTM administration did not influence the recovery from DIC and overall survival. There were no severe hemorrhagic events after rTM administration or deterioration of bleeding tendency that led to discontinuation of rTM. Discussion and Conclusion: The recovery rate from hematological malignancy-induced DIC in the current cohort was comparable to that of rTM-treated DIC group (66%) and can be superior to that of heparin-treated DIC group (50%) in a previously reported phase III trial (Saito et al, J Thromb Haemost 2006). Although the use of heparin has fostered bleeding tendency in a number of previous DIC reports, bleeding tendency was reduced after rTM administration in all the DIC episodes analyzed with the current cohort. Therefore, this analysis traced the core conclusion of the previous phase III trial, emphasizing that rTM can be an effective anti-DIC agent without causing adverse hemorrhagic event even in DIC cases with preexisting bleeding tendency. However, the result was still significantly worse in infection-induced DIC secondary to hematological malignancies. Disclosures: Chiba: Asahi Kasei Pharma: Research Funding.

Surgery-first treatment improves clinical results in infective endocarditis complicated with disseminated intravascular coagulation†

2019 ◽  
Vol 56 (4) ◽  
pp. 785-792 ◽  
Author(s):  
Junya Yokoyama ◽  
Daisuke Yoshioka ◽  
Koichi Toda ◽  
Ryohei Matsuura ◽  
Kota Suzuki ◽  
...  
Keyword(s):  
Overall Survival ◽  
Infective Endocarditis ◽  
Medical Treatment ◽  
Disseminated Intravascular Coagulation ◽  
Treatment Strategy ◽  
Survival Rates ◽  
Valve Surgery ◽  
Intravascular Coagulation ◽  
Surgery First ◽  
Overall Survival Rates

Abstract OBJECTIVES: Infective endocarditis (IE) is a critical infection with a high mortality rate, and it usually causes sepsis. Though disseminated intravascular coagulation (DIC) sometimes occurs in IE patients, no definitive treatment strategy for IE patients with DIC as a complication exists. Therefore, we evaluated the prevalence, surgical results and treatment strategy for IE complicated with DIC. METHODS: Between 2009 and 2017, a total of 585 patients undergoing valve surgery for active IE were enrolled at 14 institutions, of whom 116 (20%) had DIC as a complication. For further evaluation, we divided DIC patients into medical treatment-first (n = 45, group M) and valve surgery-first (n = 51, group S) groups after excluding 20 patients with intracranial haemorrhage. RESULTS: The overall survival rates at 1 and 5 years were 91% and 85% in the non-DIC group and 65% and 55% in the DIC group, respectively (P < 0.001). Recurrence-free survival rates at 1 and 5 years were 99% and 95% in the non-DIC group and 94% and 74% in the DIC group, respectively (P < 0.001). The overall survival rates at 1 and 5 years were 77% and 64% in group S and 51% and 46% in group M, respectively (P = 0.032). Multivariable analysis revealed that ‘medical treatment first’ was an exclusive independent risk factor [hazards ratio 2.26 (1.13–4.75), P = 0.024] for overall mortality. CONCLUSIONS: Mortality and IE recurrence were statistically significantly higher in DIC patients. Valve surgery should not be delayed because most patients proceeding with medical treatment eventually require emergency surgery and their clinical outcomes are worse than those of patients undergoing early surgery.

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.

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 Disseminated intravascular coagulation in an under-recognised zoonotic infection

2017 ◽  
Vol 16 (3) ◽  
pp. 138-141
Author(s):  
Sarah Lawrence ◽  
◽  
Andrew Claxton ◽  
Mark Holland ◽  
Jack Hodd ◽  
...  
Keyword(s):  
Severe Sepsis ◽  
Disseminated Intravascular Coagulation ◽  
Platelet Transfusion ◽  
Purpura Fulminans ◽  
Blood Cultures ◽  
Organ Support ◽  
Zoonotic Infection ◽  
Intravascular Coagulation ◽  
Prompt Treatment ◽  
History Of

A 51 year old man presented with severe sepsis, disseminated intravascular coagulation (DIC) and multiorgan dysfunction after a 24 hour history of diarrhoea and malaise. Despite fluid resuscitation and receiving a platelet transfusion, freshfrozen plasma and intravenous broad-spectrum antibiotics, he remained anuric with a worsening metabolic acidosis. He was transferred to critical care for organ support including renal replacement therapy. He subsequently developed purpura fulminans. Blood cultures were positive for Captocytophaga carnimorsis, a gram-negative canine zoonosis that is an underdiagnosed cause of severe sepsis, for which DIC at presentation is characteristic. Treatment is with penicillins and fluoroquinolones. Identification of risk factors for unusual organisms and recognition of DIC allowing prompt treatment is critical for the acute physician.

Sign in / Sign up

Export Citation Format

Share Document