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Background Little evidence supports anticoagulant therapy as effective adjuvant therapy to reduce mortality overall in sepsis. However, several studies suggest that anticoagulant therapy may reduce mortality in specific patients. This study aimed to identify a subset of patients with high benefit profiles for anticoagulant therapy against sepsis. Methods This post hoc subgroup analysis of a nationwide multicentre retrospective registry was conducted in 42 intensive care units in Japan. Consecutive adult patients with sepsis were included. Treatment effects of anticoagulants, e.g. antithrombin, recombinant thrombomodulin, heparin, and protease inhibitors, were evaluated by stratifying patients according to disseminated intravascular coagulation (DIC) and Sequential Organ Failure Assessment (SOFA) score. Intervention effects of anticoagulant therapy on in-hospital mortality and bleeding complications were analysed using Cox regression analysis stratified by propensity scores. Results Participants comprised 2663 consecutive patients with sepsis; 1247 patients received anticoagulants and 1416 received none. After adjustment for imbalances, anticoagulant administration was significantly associated with reduced mortality only in subsets of patients diagnosed with DIC, whereas similar mortality rates were observed in non-DIC subsets with anticoagulant therapy. Favourable associations between anticoagulant therapy and mortality were observed only in the high-risk subset (SOFA score 13–17; adjusted hazard ratio 0.601; 95 % confidence interval 0.451, 0.800) but not in the subsets of patients with sepsis with low to moderate risk. Although the differences were not statistically significant, there was a consistent tendency towards an increase in bleeding-related transfusions in all SOFA score subsets. Conclusions The analysis of this large database indicates anticoagulant therapy may be associated with a survival benefit in patients with sepsis-induced coagulopathy and/or very severe disease. Trial registration University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR ID: UMIN000012543 ). Registered on 10 December 2013.

Introduction The safety and efficacy of recombinant human soluble thrombomodulin (rhTM) have been demonstrated, with promising evidence suggestive of efficacy for patients with severe sepsis involving coagulopathy in a phase IIb randomized controlled trial. However, the benefit profiles of rhTM have not been elucidated. The purpose of this study was to explore whether patients with greater disease severity, determined according to the Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores, would experience treatment benefit from rhTM administration. Methods This was a post hoc , subgroup analysis of a multicenter retrospective cohort study conducted in three Japanese tertiary referral hospitals. Patients with sepsis-induced disseminated intravascular coagulation (DIC) who required ventilator management were included. We stratified patients into several strata according to disease severity, determined by APACHE II and SOFA scores, using classification and regression trees for survival data. Intervention effects, expressed as hazard ratios (HR), were analyzed using Cox regression analysis adjusted for a propensity model to detect subgroup heterogeneity of the effects of rhTM on in-hospital mortality. Results Participants were 162 patients with sepsis-induced DIC; 68 of these patients received rhTM and 94 did not. After adjusting for imbalances, rhTM administration was significantly associated with reduced mortality in high-risk patients (APACHE II: 24 to 29; HR: 0.281; 95% confidence interval (CI): 0.093 to 0.850; P  = 0.025). A similar nonsignificant tendency was observed in the very high-risk subset (APACHE II: ≥30; HR: 0.529; 95% CI: 0.202 to 1.387; P  = 0.195) but was not evident in the moderate-risk subset of patients (APACHE II: <24; HR: 0.814; 95% CI: 0.351 to 1.884; P  = 0.630). A similar tendency was observed in analysis of SOFA scores (moderate-risk subset (SOFA: <11), P  = 0.368; high-risk subset (SOFA: ≥11), P  = 0.042). Conclusions Survival benefit was observed with rhTM treatment in sepsis-induced DIC and high risk of death according to baseline APACHE II and SOFA scores.

The mortality rate of sepsis-associated disseminated intravascular coagulation (DIC) is high. This study aimed to explore the efficacy of therapeutic plasma exchange (TPE) in sepsis-associated DIC patients by improving endothelial function. A total of 112 sepsis-associated DIC patients were randomly divided into the TPE group (n = 40), the heparin (HP) group (n = 36), and the SHAM group (n = 36). The SHAM group received conventional treatment; the HP group was treated with HP based on conventional treatment; and the TPE group received conventional treatment plus TPE. The differences in thromboelastogram (TEG), platelet (PLT), coagulation function, and the endothelial cell (EC) injury biomarkers at 6 h, 24 h, 48 h, 72 h, and 7 days after TPE were compared among the three groups, and the three groups were compared in terms of Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Sepsis-Related Organ Failure Assessment (SOFA) score, the length of intensive care unit (ICU) hospitalization, 28-day mortality rate, 28-day cumulative survival rate, the incidence of bleeding events, the incidence of acute kidney injury (AKI), and acute respiratory distress syndrome (ARDS). The efficacy of TPE is superior to the HP in increasing PLT, improving coagulation function, increasing the 28-day cumulative survival rate, and reducing the length of ICU hospitalization, 28-day mortality, and the incidence of bleeding events, AKI, and ARDS with statistically significant differences (P < .05). Moreover, the effect of TPE outperforms HP on the EC injury biomarkers with statistically significant differences (P < .05). Our results suggest that TPE may be more effective than HP in the treatment of patients with sepsis-associated DIC. The possible mechanism is via improving endothelial function.

ObjectiveTo determine whether treatment with recombinant human thrombomodulin (rhTM) increases survival among patients with severe septic-induced disseminated intravascular coagulation (DIC).DesignSingle-centre, open-label, randomised controlled trial.SettingSingle tertiary hospital.Participant92 patients with severe septic-induced DIC.InterventionsPatients with DIC scores ≥4, as defined by the Japanese Association of Acute Medicine, were diagnosed with DIC. The envelope method was used for randomisation. The treatment group (rhTM group, n=47) was intravenously treated with rhTM within 24 hours of admission (day 0), and the control group (n=45) did not receive any anticoagulants, except in cases of deep venous thrombosis and pulmonary embolism.Primary and secondary measurementsData were collected on days 0 (admission), 1, 2, 3, 5, 7 and 10. The primary outcome was survival at 28 and 90 days. The secondary end points comprised changes in DIC scores, platelet counts, d-dimer, antithrombin III and C reactive protein levels, and Sequential Organ Failure Assessment (SOFA) scores. All analyses were conducted on an intent-to-treat basis.Main resultsThe 28-day survival rates were 84% and 83% in the control and rhTM groups, respectively (p=0.745, log-rank test). The 90-day survival rates were 73% and 72% in the control and rhTM groups, respectively (p=0.94, log-rank test). Meanwhile, the rates of recovery from DIC (<4) were significantly higher in the rhTM group than in the control group (p=0.001, log-rank test). Relative change from baseline of d-dimer levels was significantly lower in the rhTM group than in the control group, on days 3 and 5.ConclusionsrhTM treatment decreased d-dimer levels and facilitated DIC recovery in patients with severe septic-induced DIC. However, the treatment did not improve survival in this cohort.Trial registration numberUMIN000008339.

Recombinant human thrombomodulin (rhTM) is often used concomitantly with antithrombin (AT) to treat disseminated intravascular coagulation (DIC). This observational study aimed to investigate the efficacy and safety of AT+rhTM combination therapy. One hundred twenty-nine patients with severe sepsis and DIC participated in this study. Of these, 78 patients were treated with AT+rhTM (AT+rhTM group) and 51 patients were treated with AT alone (AT group). We compared coagulation and inflammation markers, Sequential Organ Failure Assessment score, and DIC score at day 0 (baseline) and day 7 between the 2 groups. Bleeding events and 28-day mortality were also compared. Platelet counts and D-dimer levels at day 7 significantly improved in the AT+rhTM group compared with the AT group, and 28-day mortality was significantly lower in the AT+rhTM group than in the AT group (AT+rhTM: 15.4% vs AT: 29.4%). During the study period, the incidence of bleeding complications was similar in both groups (AT+rhTM: 6.4% vs AT: 7.8%). Compared with AT monotherapy, combination therapy with AT and rhTM may be more effective in improving platelet counts and D-dimer levels, as well as reducing mortality, in patients with severe sepsis-associated DIC.

PurposeCovid-19 is a global threat that pushes health care to its limits. Since there is neither a vaccine nor a drug for Covid-19, people with an increased risk for severe and fatal courses of disease particularly need protection. Furthermore, factors increasing these risks are of interest in the search of potential treatments. A systematic literature review on the risk factors of severe and fatal Covid-19 courses is presented.MethodsThe review is carried out on PubMed and a publicly available preprint dataset. For analysis, risk factors are categorized and information regarding the study such as study size and location are extracted. The results are compared to risk factors listed by four public authorities from different countries.ResultsThe 28 records included, eleven of which are preprints, indicate that conditions and comorbidities connected to a poor state of health such as high age, obesity, diabetes and hypertension are risk factors for severe and fatal disease courses. Furthermore, severe and fatal courses are associated with organ damages mainly affecting the heart, liver and kidneys. Coagulation dysfunctions could play a critical role in the organ damaging. Time to hospital admission, tuberculosis, inflammation disorders and coagulation dysfunctions are identified as risk factors found in the review but not mentioned by the public authorities.ConclusionFactors associated with increased risk of severe or fatal disease courses were identified, which include conditions connected with a poor state of health as well as organ damages and coagulation dysfunctions. The results may facilitate upcoming Covid-19 research.

Background COVID-19 is a viral respiratory disease caused by the severe acute respiratory syndrome-Coronavirus type 2 (SARS-CoV-2). Patients with this disease may be more prone to venous or arterial thrombosis because of the activation of many factors involved in it, including inflammation, platelet activation and endothelial dysfunction. Interferon gamma inducible protein-10 (IP-10), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein 1-alpha (MIP1α) are cytokines related to thrombosis. Therefore, this study focused on these three indicators in COVID-19, with the hope to find biomarkers that are associated with patients’ outcome. Methods This is a retrospective single-center study involving 74 severe and critically ill COVID-19 patients recruited from the ICU department of the Tongji Hospital in Wuhan, China. The patients were divided into two groups: severe patients and critically ill patients. The serum IP-10, MCP-1 and MIP1α level in both groups was detected using the enzyme-linked immunosorbent assay (ELISA) kit. The clinical symptoms, laboratory test results, and the outcome of COVID-19 patients were retrospectively analyzed. Results The serum IP-10 and MCP-1 level in critically ill patients was significantly higher than that in severe patients ( P  < 0.001). However, no statistical difference in MIP1α between the two groups was found. The analysis of dynamic changes showed that these indicators remarkably increased in patients with poor prognosis. Since the selected patients were severe or critically ill, no significant difference was observed between survival and death. Conclusions IP-10 and MCP-1 are biomarkers associated with the severity of COVID-19 disease and can be related to the risk of death in COVID-19 patients.

Disseminated intravascular coagulation (DIC) is a common complication in sepsis patients which exacerbates patient outcomes. The prevalence and outcomes of DIC in sepsis is wide-ranging and highly depends on the severity of the disease and diagnostic approaches utilized. Varied diagnostic criteria of DIC have been developed and their performance in diagnosis and prognosis is not consistent. Therefore, this study aimed to determine the score positivity rate and performance of different DIC scoring systems in predicting mortality in sepsis patients. Four databases, including Medline (through PubMed), Scopus, Embase, and Web of Science were searched for studies that determined DIC in sepsis patients using the three scoring systems namely: the International Society on Thrombosis and Hemostasis DIC (ISTH-DIC) criteria, the Japanese association for acute medicine DIC (JAAM-DIC) criteria, and the sepsis-induced coagulopathy (SIC) criteria. A random-effect meta-analysis was performed with a 95% confidence interval (CI). Subgroup analysis was conducted in view of geographic region and sepsis stages. the protocol was submitted to the Prospective Register for Systematic Reviews (PROSPERO) with an identifier (CRD42023409614). Twenty-one studies, published between 2009 and 2024, comprising 9319 sepsis patients were included. The pooled proportion of cases diagnosed as positive using ISTH-DIC criteria, JAAM-DIC criteria, and SIC were 28% (95% CI: 24-34%), 55% (95% CI:42-70%), and 57% (95% CI: 52-78%), respectively. The pooled mortality rates were 44% (95% CI:33-53%), 37% (95% CI: 29-46%), and 35% (95% CI: 29-41%), respectively. The pooled sensitivity and specificity of ISTH-DIC to predict mortality were 0.43 (95% CI: 0.34-0.52), and 0.81 (95% CI: 0.74-0.87), respectively, while for JAAM-DIC it was 0.73 (95% CI: 0.57-0.85) and 0.46 (95% CI: 0.28-0.65), respectively. Pooled sensitivity and specificity for SIC were 0.71 (95% CI: 0.57-0.82) and 0.49 (95% CI: 0.31-0.66), respectively. The SIC and JAAM-DIC scores exhibited higher sensitivity to identify patients with coagulopathy and predict patient outcomes, and thus are valuable to identify patients for possible treatment at an early stage. The ISTH-DIC score perhaps identified patients at later stages and demonstrated better specificity to predict disease outcomes. Thus, early identification of patients using the SIC and JAAM-DIC scores and later confirmation using the ISTH-DIC score would be beneficial approach for improved management of patients with sepsis.

Despite the established link between sepsis and disseminated intravascular coagulation (DIC), data on the prevalence of DIC, associated factors and patient outcomes in sepsis patients are inadequate in resource-limited settings. Therefore, the present study aimed to determine the magnitude of DIC and associated factors and mortality and predictors in septic adults admitted to intensive care units (ICUs). A prospective longitudinal study involving adults admitted to intensive care units was conducted. A structured checklist and questionnaire were used to collect patient demographic and clinical data. Blood samples were collected on days 1, 3, and 5 of admission for all laboratory analyses. A DIC diagnosis was made on the basis of the Japanese Association for Acute Medicine (JAAM) score. Descriptive statistics, multivariable logistic regression analysis, receiver operating characteristic (ROC) curve analysis and Kaplan‒Meier survival analysis were employed in this study. The overall prevalence of DIC in sepsis patients was 38 (25.7%). There were 24 (16.2%) patients who developed DIC on day 1 of admission, while 20 (19.4%) and 9 (12.9%) patients developed DIC on day 3 and day 5 of admission, respectively. Increased aspartate transaminase (AST) (AOR: 4.39; 95% CI: 1.75-11.01), thrombocytopenia (AOR: 6.04; 95% CI: 2.41-15.12), and prolonged prothrombin time (PT) (AOR: 3.40; 95% CI: 1.36-8.51) were independent predictors of DIC in sepsis patients. There was no statistically significant difference in survival between patients with and without DIC (p < 0.328). The JAAM score at ICU admission predicted ICU mortality (AUC: 0.787; 95% CI: 0.624-0.950). A quarter of ICU-admitted septic adults developed DIC. The incidence was notably greater by the third day after admission, highlighting the importance of closely monitoring these patients for DIC progression. Elevated AST liver enzyme levels, thrombocytopenia, and prolonged PT are linked to the development of DIC. Changes in these variables could prompt further examination for DIC. The mortality rate did not significantly differ between septic patients with and without DIC. The JAAM score used to diagnose DIC in sepsis patients can serve as a predictor of ICU mortality in sepsis patients with DIC.

We investigated the epidemiology and outcome of disseminated intravascular coagulation (DIC) in patients with sepsis. We analyzed data from a multicenter observational study (Japan Septic Disseminated Intravascular Coagulation [JSEPTIC-DIC] study) conducted in 42 intensive care units in Japan. DIC scores were calculated using two scoring systems: the International Society on Thrombosis and Haemostasis (ISTH) and Japanese Association for Acute Medicine (JAAM) criteria. We compared demographics and clinical characteristics of patients with and without DIC, and performed multivariable logistic regression analyses to assess the association of diagnosis and scores for DIC with in-hospital mortality. Of 1895 eligible patients, 1162 (61%) and 554 patients (29%) were diagnosed as having DIC by the JAAM and ISTH criteria, respectively. Patients with DIC had higher in-hospital mortality compared with those without DIC (33% vs. 20% in JAAM and 38% vs. 24% in ISTH). However, in multivariable analysis, the JAAM score (odds ratio 1.026, 95% confidence interval 0.958–1.097; p = 0.465) and the ISTH score (odds ratio 1.049, 95% confidence interval 0.969–1.135; p = 0.238) did not have an independent association with in-hospital mortality. Patients with sepsis and DIC have high mortality. However, the DIC are not independently associated with in-hospital mortality. •We investigated the epidemiology and outcome of disseminated intravascular coagulation (DIC) in patients with sepsis.•We analyzed data from a multicenter observational study (JSEPTIC-DIC) conducted in 42 ICUs in Japan.•Of 1895 eligible patients, 61% and 29% were diagnosed as having DIC by the JAAM and ISTH criteria, respectively.•DIC had higher in-hospital mortality compared with those without DIC.•In multivariable analysis, both scores did not have an independent association with in-hospital mortality.