scholarly journals Advance in the Management of Sepsis-Induced Coagulopathy and Disseminated Intravascular Coagulation

2019 ◽  
Vol 8 (5) ◽  
pp. 728 ◽  
Author(s):  
Toshiaki Iba ◽  
Jerrold Levy ◽  
Aditya Raj ◽  
Theodore Warkentin
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Statistical Significance ◽  
Phase Iii ◽  
Endothelial Glycocalyx ◽  
Absolute Difference ◽  
Sepsis Management ◽  
Intravascular Coagulation ◽  
Intravascular Thrombosis ◽  
Increased Risk ◽  
Recombinant Thrombomodulin

Coagulopathy commonly occurs in sepsis as a critical host response to infection that can progress to disseminated intravascular coagulation (DIC) with an increased mortality. Recent studies have further defined factors responsible for the thromboinflammatory response and intravascular thrombosis, including neutrophil extracellular traps, extracellular vesicles, damage-associated molecular patterns, and endothelial glycocalyx shedding. Diagnosing DIC facilitates sepsis management, and is associated with improved outcomes. Although the International Society on Thrombosis and Haemostasis (ISTH) has proposed criteria for diagnosing overt DIC, these criteria are not suitable for early detection. Accordingly, the ISTH DIC Scientific Standardization Committee has proposed a new category termed “sepsis-induced coagulopathy (SIC)” to facilitate earlier diagnosis of DIC and potentially more rapid interventions in these critically ill patients. Therapy of SIC includes both treatment of the underlying infection and correcting the coagulopathy, with most therapeutic approaches focusing on anticoagulant therapy. Recently, a phase III trial of recombinant thrombomodulin was performed in coagulopathic patients. Although the 28-day mortality was improved by 2.6% (absolute difference), it did not reach statistical significance. However, in patients who met entry criteria for SIC at baseline, the mortality difference was approximately 5% without increased risk of bleeding. In this review, we discuss current advances in managing SIC and DIC.

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.

scholarly journals Predictors of Disseminated Intravascular Coagulation in Patients with Septic Shock

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Diana J. Kelm ◽  
Juan Carlos Valerio-Rojas ◽  
Javier Cabello-Garza ◽  
Ognjen Gajic ◽  
Rodrigo Cartin-Ceba
Keyword(s):  
Septic Shock ◽  
Antiplatelet Therapy ◽  
Disseminated Intravascular Coagulation ◽  
Tertiary Care ◽  
Multivariate Logistic Regression Model ◽  
Care Hospital ◽  
Clinical Predictors ◽  
Intravascular Coagulation ◽  
Early Goal Directed Therapy ◽  
Increased Risk

Purpose. The goal of this study was to identify potential clinical predictors for the development of disseminated intravascular coagulation (DIC) in patients with septic shock. Material and Methods. We performed a retrospective analysis of a cohort of adult (>18 years of age) patients with septic shock admitted to a medical ICU in a tertiary care hospital from July 2005 until September 2007. A multivariate logistic regression model was used to determine the association of risk factors with overt DIC. Results. In this study, a total of 390 patients with septic shock were analyzed, of whom 66 (17%) developed overt DIC. Hospital mortality was significantly greater in patients who developed overt DIC (68% versus 38%, P<0.001). A delay in the timing of antibiotics was associated with an increased risk of the development of overt DIC (P<0.001). Patients on antiplatelet therapy prior to hospital admission and who that received adequate early goal-directed therapy (EGDT) were associated with a decreased risk of overt DIC (P<0.001). Conclusions. In our cohort of patients with septic shock, there was a risk reduction for overt DIC in patients on antiplatelet therapy and adequate EGDT, while there was an increased risk of DIC with antibiotic delay.

scholarly journals Disseminated Intravascular Coagulation: An Update on Pathogenesis, Diagnosis, and Therapeutic Strategies

2018 ◽  
Vol 24 (9_suppl) ◽  
pp. 8S-28S ◽  
Author(s):  
Chrysoula Papageorgiou ◽  
Georges Jourdi ◽  
Eusebe Adjambri ◽  
Amanda Walborn ◽  
Priya Patel ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Severe Sepsis ◽  
Disseminated Intravascular Coagulation ◽  
Bleeding Risk ◽  
Therapeutic Strategies ◽  
Phase Iii ◽  
Clotting Factor ◽  
Clotting Factors ◽  
Intravascular Coagulation ◽  
Positive Effects

Disseminated intravascular coagulation (DIC) is an acquired clinicobiological syndrome characterized by widespread activation of coagulation leading to fibrin deposition in the vasculature, organ dysfunction, consumption of clotting factors and platelets, and life-threatening hemorrhage. Disseminated intravascular coagulation is provoked by several underlying disorders (sepsis, cancer, trauma, and pregnancy complicated with eclampsia or other calamities). Treatment of the underlying disease and elimination of the trigger mechanism are the cornerstone therapeutic approaches. Therapeutic strategies specific for DIC aim to control activation of blood coagulation and bleeding risk. The clinical trials using DIC as entry criterion are limited. Large randomized, phase III clinical trials have investigated the efficacy of antithrombin (AT), activated protein C (APC), tissue factor pathway inhibitor (TFPI), and thrombomodulin (TM) in patients with sepsis, but the diagnosis of DIC was not part of the inclusion criteria. Treatment with APC reduced 28-day mortality of patients with severe sepsis, including patients retrospectively assigned to a subgroup with sepsis-associated DIC. Treatment with APC did not have any positive effects in other patient groups. The APC treatment increased the bleeding risk in patients with sepsis, which led to the withdrawal of this drug from the market. Treatment with AT failed to reduce 28-day mortality in patients with severe sepsis, but a retrospective subgroup analysis suggested possible efficacy in patients with DIC. Clinical studies with recombinant TFPI or TM have been carried out showing promising results. The efficacy and safety of other anticoagulants (ie, unfractionated heparin, low-molecular-weight heparin) or transfusion of platelet concentrates or clotting factor concentrates have not been objectively assessed.

scholarly journals The Suprapharmacologic Dosing of Antithrombin Concentrate for Staphylococcus Aureus-Induced Disseminated Intravascular Coagulation in Guinea Pigs: Substantial Reduction in Mortality and Morbidity

Blood ◽  
1997 ◽  
Vol 89 (12) ◽  
pp. 4393-4401 ◽  
Author(s):  
Craig M. Kessler ◽  
ZhaoCheng Tang ◽  
Helena M. Jacobs ◽  
Linda M. Szymanski
Keyword(s):  
Staphylococcus Aureus ◽  
Disseminated Intravascular Coagulation ◽  
Guinea Pigs ◽  
Degradation Products ◽  
Statistical Significance ◽  
Substantial Reduction ◽  
Mortality And Morbidity ◽  
Sterile Saline ◽  
Intravascular Coagulation ◽  
Fibrin Formation

Abstract An animal model of gram-positive septicemia was developed to evaluate the effects of antithrombin (AT) concentrates on morbidity, mortality, and laboratory consequences of disseminated intravascular coagulation (DIC). DIC was induced in guinea pigs by infusing Staphylococcus aureus (SA) isolated from blood cultures of patients with DIC (DIC-SA) or without DIC (non–DIC-SA). The non–DIC-SA animals and animals infused with sterile saline served as controls. Varying doses of AT were administered either 30 minutes or 24 hours after infusion of SA. DIC was confirmed within 4 hours by changes in prothrombin time, activated partial thromboplastin time, fibrinogen, fibrinogen-fibrin degradation products, and AT activity. Clinical bleeding was also evident. Mortality of untreated DIC-SA animals was 36% within 24 hours and up to 75% by 72 hours. Intervention with any dose of AT between 125 and 1,000 IU/kg 30 minutes after DIC-SA infusion was associated with 100% survival (P ≤ .05 in the 250 IU/kg group) and sustained increases in AT activity and fibrinogen concentrations (P ≤ .05). When AT was administered in combination with low molecular weight heparin (LMWH) or if LMWH was adminstered alone, mortality from DIC-SA was slightly, but not significantly reduced compared with untreated DIC-SA. Gross hemorrhage was observed premortem and at autopsy in all of the DIC-SA animals but in substantially fewer animals that received AT (P ≤ .001 in the 250, 500, and 1,000 IU/kg groups). In contrast, groups treated with LMWH, alone or with AT, experienced hemorrhage and appeared to develop pathologic DIC. Fibrin formation in end-organs was detected in all guinea pigs in the untreated DIC-SA group and in the groups treated with 125 IU/kg AT and LMWH alone. AT doses between 250 and 1,000 IU/kg administered 30 minutes after DIC-SA infusion prevented fibrin formation in end-organs (P ≤ .001 in the 250 and 1,000 IU/kg groups). AT administered 24 hours after DIC-SA could not reverse pre-existing histopathologic evidence of DIC but favorably affected survival, which reached statistical significance in the 1,000 IU/kg AT group (P ≤ .025). In summary, suprapharmacologic doses of AT concentrate significantly decreased morbidity and mortality and ameliorated adverse changes in laboratory measures induced by DIC-SA in this guinea pig model and were not associated with untoward hemorrhagic complications. These findings provide justification for studying the use of AT therapy in patients with DIC-SA.

scholarly journals Purpura Fulminans following Thermal Injury

2013 ◽  
Vol 2013 ◽  
pp. 1-3 ◽  
Author(s):  
Jiongyu Hu ◽  
Xupin Jiang ◽  
Ting He ◽  
Qizhi Luo
Keyword(s):  
Organ Dysfunction ◽  
Disseminated Intravascular Coagulation ◽  
Thermal Injury ◽  
Purpura Fulminans ◽  
Multiple Organ ◽  
Multiple Organ Dysfunction ◽  
Small Children ◽  
Intravascular Coagulation ◽  
Intravascular Thrombosis ◽  
First Case

Purpura fulminans is a rare syndrome of intravascular thrombosis and hemorrhagic infarction of the skin, which is an unusual cutaneous manifestation of disseminated intravascular coagulation. It often occurs in small children and babies due to infection and/or sepsis, rarely in adults in clinic. We report the first case of deadly purpura fulminans following thermal injury in a 64-year-old Chinese woman. The purpura developed sharply and aggravated multiple organ dysfunction. The patient died of purpura fulminans, disseminated intravascular coagulation, and multiple organ dysfunction syndrome.

scholarly journals Mortality in Patients With Septic Shock by Multidrug Resistant Bacteria

2017 ◽  
Vol 34 (1) ◽  
pp. 48-54 ◽  
Author(s):  
Stefano Busani ◽  
Giulia Serafini ◽  
Elena Mantovani ◽  
Claudia Venturelli ◽  
Maddalena Giannella ◽  
...  
Keyword(s):  
Septic Shock ◽  
Statistical Significance ◽  
Multidrug Resistant ◽  
Immunoglobulin M ◽  
University Hospital ◽  
Resistant Bacteria ◽  
Sepsis Management ◽  
Risk Of Death ◽  
Increased Risk ◽  
The Impact

Background: Patients with septic shock by multidrug resistant (MDR) microorganism maybe considered a specific population of critical patients at very high risk of death in whom the effects of standard sepsis treatment has never been assessed. The objective of this retrospective analysis was to evaluate the risk factors for 30-day mortality and the impact of sepsis management in patients with septic shock caused by MDR bacteria. Methods: Patients with septic shock by MDR bacteria admitted to the mixed intensive care unit (ICU) of Modena University Hospital during a 6-year period were studied. The clinical and microbiological characteristics and sepsis treatments provided were analyzed and compared between survivors (S) and nonsurvivors (NS) at 30 days after septic shock appearance. Results: Ninety-four patients were studied. All therapeutic interventions applied to patients during their ICU stay did not show statistical significance between S and NS groups, except for administration of immunoglobulin M (IgM) preparation which were provided more frequently in S group ( P < .05). At the multivariate adjusted analysis, preexisting cancer (odds ratio [OR] = 2.965) and Acinetobacter baumannii infections (OR = 3.197) were independently correlated with an increased risk of 30-day mortality, whereas treatment with IgM preparation was protective (OR = 0.283). Conclusions: This retrospective study showed that in patients with septic shock caused by MDR bacteria, history of cancer and infection sustained by A baumannii increase the risk of mortality and that standard sepsis treatments do not seem to provide any protective effect. Adjunctive therapy with IgM preparation seems to be beneficial, but further appropriate studies are needed to confirm the results observed.

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