ABSTRACT-Supplemental doses of antithrombin (AT) are widely used to treat sepsis-induced disseminated intravascular coagulation (DIC) in Japan. However, evidence on the benefits of ATsupplementation for DIC is insufficient. This multicenter retrospective observational study aimed to clarify the effect of AT supplementation on sepsis-induced DIC using propensity score analyses. Data from 3,195 consecutive adult patients admitted to 42 intensive care units for severe sepsis treatment were retrospectively analyzed; 1,784 patients were diagnosed with DIC (n ¼ 715, AT group; n ¼ 1,069, control group). Inverse probability of treatment-weighted propensity score analysis indicated a statistically significant association between AT supplementation and lower in-hospital all-cause mortality (n ¼ 1,784, odds ratio [95% confidence intervals]: 0.748 [0.572-0.978], P ¼ 0.034). However, quintile-stratified propensity score analysis (n ¼ 1,784, odds ratio: 0.823 [0.646-1.050], P ¼ 0.117) and propensity score matching analysis (461 matching pairs, odds ratio: 0.855 [0.649-1.125], P ¼ 0.263) did not show this association. In the early days after intensive care unit admission, the survival rate was statistically higher in the propensity score-matched AT group than in the propensity score-matched control group (P ¼ 0.007). In DIC patients without concomitant heparin administration, similar results were observed. In conclusion, AT supplementation may be associated with reduced in-hospital all-cause mortality in patients with sepsis-induced DIC. However, the statistical robustness of this connection was not strong. In addition, although the number of transfusions needed in patients with AT supplementation increased, severe bleeding complications did not.

Severe sepsis is a major concern in the intensive care unit (ICU), although there is very little epidemiological information regarding severe sepsis in Japan. This study evaluated 3195 patients with severe sepsis in 42 ICUs throughout Japan. The patients with severe sepsis had a mean age of 70 ± 15 years and a mean Acute Physiology and Chronic Health Evaluation II score of 23 ± 9. The estimated survival rates at 28 and 90 days after ICU admission were 73.6 and 56.3 %, respectively.Electronic supplementary materialThe online version of this article (doi:10.1186/s40560-016-0169-9) contains supplementary material, which is available to authorized users.

Rotational thromboelastometry (ROTEM), known as point-of-care testing, has been incorporated into various kinds of postsurgical management. However, the utility of ROTEM for rapid diagnosis of sepsis-induced disseminated intravascular coagulation (DIC) has not been investigated. This retrospective study includes 13 sepsis patients who underwent ROTEM in our emergency department in 2013. All patients were divided into two groups on the basis of the presence of DIC diagnosed by the Japanese Association for Acute Medicine (JAAM) DIC score. We evaluated the demographics, clinical characteristics, laboratory data, ROTEM test and outcomes for each patient. The correlations between JAAM DIC score and significantly different parameters by univariate analysis and receiver operating characteristic (ROC) analysis were performed to assess the accuracy of the variables. There were seven and six patients in the DIC group and non-DIC group, respectively. The DIC group showed significantly longer prothrombin times, international normalized ratio of prothrombin time and clotting times (CTs) in the EXTEM test, and higher fibrinogen and fibrin degradation products and D-dimer. The CT in EXTEM test was correlated more with JAAM DIC score (r = 0.798), than the standard coagulation test. These parameters were accurate predictors in the diagnosis of septic DIC, with an AUC of 0.952, and a cut-off value of more than 46.0 s, resulting in a sensitivity of 100.0% and a specificity of 83.3%. CT in the EXTEM test was a single reliable indicator of sepsis-induced DIC diagnosed by the JAAM DIC score, and strongly associated with severity of DIC.

It is well known that coagulopathy is observed in patients with out-of-hospital cardiac arrest (OHCA). Thrombolytic therapy for those patients has been controversial until now. The purpose of this study was to identify a significant predictor for return of spontaneous circulation (ROSC) of OHCA patients in the emergency department (ED) using whole blood viscoelastic testing. Adult non-trauma OHCA patients transported to our hospital that underwent thromboelastometry (ROTEM) during cardiopulmonary resuscitation between January 2013 and December 2015 were enrolled in this study. We divided patients into two groups based on the presence or absence of ROSC, and performed statistical analysis utilizing patient characteristics, prehospital data, laboratory data, and ROTEM data. Seventy-five patients were enrolled. The ROSC group and non-ROSC group included 23 and 52 patients, respectively. The logistic regression analysis, utilizing significant parameters by univariate analysis, demonstrated that lactate level [odds ratio (OR) 0.880, 95% confidence interval (CI) 0.785–0.986, p = 0.028] and A30 of EXTEM test [OR 1.039, 95% CI 1.010–1.070, p = 0.009] were independent risk factors for ROSC. The cut-off values of lactate and A30 in EXTEM were 12.0 mmol/L and A 48.0 mm, respectively. We defined a positive prediction for ROSC if the patient presented lower lactate level (<12.0 mmol/L) and higher A30 of EXTEM (≥48.0 mm) with high specificity (94.7%) and accuracy (75.0%). The present study showed that lactate level and ROTEM parameter of clot firmness were reliable predictors of ROSC in the ED for adult patients with OHCA.

BackgroundThe administration of low-dose intravenous immunoglobulin G (IVIgG) (5 g/day for 3 days; approximate total 0.3 g/kg) is widely used as an adjunctive treatment for patients with sepsis in Japan, but its efficacy in the reduction of mortality has not been evaluated. We investigated whether the administration of low-dose IVIgG is associated with clinically important outcomes including intensive care unit (ICU) and in-hospital mortality.MethodsThis is a post-hoc subgroup analysis of data from a retrospective cohort study, the Japan Septic Disseminated Intravascular Coagulation (JSEPTIC DIC) study. The JSEPTIC DIC study was conducted in 42 ICUs in 40 institutions throughout Japan, and it investigated associations between sepsis-related coagulopathy, anticoagulation therapies, and clinical outcomes of 3195 adult patients with sepsis and septic shock admitted to ICUs from January 2011 through December 2013. To investigate associations between low-dose IVIgG administration and mortalities, propensity score-based matching analysis was used.ResultsIVIgG was administered to 960 patients (30.8%). Patients who received IVIgG were more severely ill than those who did not (Acute Physiology and Chronic Health Evaluation (APACHE) II score 24.2 ± 8.8 vs 22.6 ± 8.7, p < 0.001). They had higher ICU mortality (22.8% vs 17.4%, p < 0.001), but similar in-hospital mortality (34.4% vs 31.0%, p = 0.066). In propensity score-matched analysis, 653 pairs were created. Both ICU mortality and in-hospital mortality were similar between the two groups (21.0% vs 18.1%, p = 0.185, and 32.9% vs 28.6%, p = 0.093, respectively) using generalized estimating equations fitted with logistic regression models adjusted for other therapeutic interventions. The administration of IVIgG was not associated with ICU or in-hospital mortality (odds ratio (OR) 0.883; 95% confidence interval (CI) 0.655–1.192, p = 0.417, and OR 0.957, 95% CI, 0.724–1.265, p = 0.758, respectively).ConclusionsIn this analysis of a large cohort of patients with sepsis and septic shock, the administration of low-dose IVIgG as an adjunctive therapy was not associated with a decrease in ICU or in-hospital mortality.Trial registrationUniversity Hospital Medical Information Network Individual Clinical Trials Registry, UMIN-CTR000012543. Registered on 10 December 2013.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-017-1764-4) contains supplementary material, which is available to authorized users.

The aim of this study is to evaluate the hematological differences between septic and traumatic disseminated intravascular coagulation (DIC) using the rotational thromboelastometry (ROTEM).This retrospective study includes all sepsis or severe trauma patients transported to our emergency department who underwent ROTEM from 2013 to 2014. All patients were divided into 2 groups based on the presence of DIC diagnosed by the Japanese Association for Acute Medicine (JAAM) DIC score. We statistically analyzed the demographics, clinical characteristics, laboratory data, ROTEM findings (EXTEM and FIBTEM), and outcome.Fifty-seven patients (30 sepsis and 27 severe trauma) were included in primary analysis. Sepsis cases were significantly older and had higher systemic inflammatory response syndrome (SIRS) scores, whereas there were no significant differences in other parameters including Acute Physiology and Chronic Health Evaluation (APACHE) II score, sequential organ failure assessment (SOFA) score. Twenty-six patients (14 sepsis and 12 severe trauma) were diagnosed with DIC. The Septic DIC (S-DIC) group was significantly older and had higher DIC scores than the traumatic DIC (T-DIC) group. Hematologic examination revealed significantly higher CRP, fibrinogen, lower FDP, DD, and higher FDP/DD ratio were found in the S-DIC group in comparison with the T-DIC group. ROTEM findings showed that the A10, A20, and MCF in the FIBTEM test were significantly higher in the S-DIC group. However, no statistical differences were confirmed in the LI30, LI45, and ML in EXTEM test.The plasma fibrinogen level and fibrinogen based clot firmness in whole-blood test revealed statistical significance between septic and traumatic DIC patients.

Human in vitro and rat in vivo experimental study.

Compared with pAT, the supplementation of rAT indicates clinical effectiveness without increasing the risk of bleeding complications in adult DIC patients with low AT activity.