Japanese Association For Acute Medicine Disseminated Intravascular Coagulation Research Articles

Proposal and Validation of a Clinically Relevant Modification of the Japanese Association for Acute Medicine Disseminated Intravascular Coagulation Diagnostic Criteria for Sepsis.

Japanese Association for Acute Medicine (JAAM) disseminated intravascular coagulation (DIC) criteria were launched nearly 20 years ago. Following the revised conceptual definition of sepsis and subsequent omission of systemic inflammatory response syndrome (SIRS) score from the latest sepsis diagnostic criteria, we omitted the SIRS score and proposed a modified version of JAAM DIC criteria, the JAAM-2 DIC criteria. To validate and compare performance between new JAAM-2 DIC criteria and conventional JAAM DIC criteria for sepsis. We used three datasets containing adult sepsis patients from a multicenter nationwide Japanese cohort study (J-septic DIC, FORECAST, and SPICE-ICU registries). JAAM-2 DIC criteria omitted the SIRS score and set the cutoff value at ≥3 points. Receiver operating characteristic (ROC) analyses were performed between the two DIC criteria to evaluate prognostic value. Associations between in-hospital mortality and anticoagulant therapy according to DIC status were analyzed using propensity score weighting to compare significance of the criteria in determining introduction of anticoagulants against sepsis. Final study cohorts of the datasets included 2,154, 1,065, and 608 sepsis patients, respectively. ROC analysis revealed that curves for both JAAM and JAAM-2 DIC criteria as predictors of in-hospital mortality were almost consistent. Survival curves for the anticoagulant and control groups in the propensity score-weighted prediction model diagnosed using the two criteria were also almost entirely consistent. JAAM-2 DIC criteria were equivalent to JAAM DIC criteria regarding prognostic and diagnostic values for initiating anticoagulation. The newly proposed JAAM-2 DIC criteria could be potentially alternative criteria for sepsis management.

The Danish Disseminated Intravascular Coagulation (DANDIC) Cohort Study: Incidence and Prognosis

Introduction: Disseminated intravascular coagulation (DIC) is a serious condition with poor prognosis and limited treatment options. Despite being a devastating disorder, data on the incidence and prognosis remains limited. Previous studies are more than 10 years old, were limited to selected patients e.g., patients admitted to university hospitals, and were unable to track transitions in sites of care. In this study, we examined the incidence and prognosis, including time trends, of DIC. Methods: Potential DIC cases were identified from the hospital laboratory database by coagulation biomarkers in the Central Denmark Region, Denmark. Patients were eligible for inclusion if they were above 18 years of age and had an International Society on Thrombosis and Haemostasis (ISTH) DIC score of five or higher or a Japanese Association for Acute Medicine (JAAM) DIC score of four or higher. An underlying disease compatible with DIC was also required for inclusion and was assessed by medical chart review. The underlying diseases were infection, malignant disorder, obstetric complications, trauma, cardiac arrest, and other less common conditions. Exclusion criteria were other conditions affecting the coagulation system. 6748 medical charts were reviewed, and 2565 patients were included in the cohort from January 2013 to December 2020. Incidence rates were computed by the number of cases per year divided with the midyear population in the Central Denmark Region and were age and sex standardized to the year 2020. Survival was determined by Kaplan-Meier estimates. Results: Out of the 2565 patients, the median age was 64 years (25th-75th percentile, 48-74 years) and 1439 (56.1%) were male. At inclusion 1055 patients had an ISTH DIC score of 5-6, 145 an ISTH DIC score of 7-8, 2014 a JAAM DIC score of 4-6 and 302 a JAAM DIC score of 7-8. The overall incidence rate per 100,000 person-years declined from 33.1 in 2013 [95% confidence interval (CI), 29.6 to 36.8] to 24.0 in 2020 [95% CI, 21.1 to 27.1]. Overall 30-day survival remained relatively unchanged at 65.0% in 2013 [95% CI, 59.9% to 70.6%] and 58.7% in 2020 [95% CI, 52.9% to 65.0%]. The incidence rate of patients with an ISTH score of 5-6 at baseline was 14.1 in 2013 [95% CI, 11.8 to 16.5] and 10.8 in 2020 [95% CI, 8.9 to 12.8]. The incidence rate of patients with an ISTH score of 7-8 at baseline remained nearly constant at 1.4 in 2013 [95% CI, 0.7 to 2.1] and 1.2 in 2020 [95% CI, 0.6 to 2.0]. Thirty-day survival was 56.2% [95% CI, 53.3% to 59.3%] for patients with an ISTH DIC score of 5-6 and 33.8% [95% CI, 26.9% to 42.4%] for patients with an ISTH DIC score of 7-8. Patients with JAAM DIC scores of 4-6 at baseline showed a decline in incidence rate from 25.8 in 2013 [95% CI, 22.7 to 29.9] to 19.4 in 2020 [95% CI, 16.8 to 22.1]. However, the incidence rate of patients with JAAM DIC scores of 7-8 remained steady at 3.6 in 2013 [95% CI, 2.4 to 4.8] and 2.3 in 2020 [95% CI, 1.4 to 3.2]. Patients with a JAAM DIC score of 4-6 at baseline had a 30-day survival rate of 62.2% [95% CI, 60.0% to 64.3%] while patients with a JAAM DIC score of 7-8 had a lower 30-day survival of 53.6% [95% CI, 48.3% to 59.6%]. Conclusion: The overall incidence of DIC declined during the study period, but overall mortality remained unchanged. The incidence rate was higher among patients with a low baseline ISTH or JAAM DIC score than among patients with a high baseline score. Survival rate was also higher for patients with a low DIC score at baseline, suggesting that DIC score at baseline may be a predictor of survival.

Risk factors for postoperative disseminated intravascular coagulation in surgical patients with non-occlusive mesenteric ischemia.

The prognostic impact of disseminated intravascular coagulation (DIC) in surgical patients with non-occlusive mesenteric ischemia (NOMI) is unclear. This study aimed to confirm the association between postoperative DIC and prognosis and to identify preoperative risk factors associated with postoperative DIC. This retrospective study included 52 patients who underwent emergency surgery for NOMI between January 2012 and March 2022. Kaplan-Meier curve analysis with the log-rank test was used to compare 30-day survival and hospital survival between patients with and without postoperative DIC. In addition, univariable and multivariable logistic regression analyses were performed to identify the preoperative risk factors for postoperative DIC. The 30-day and hospital mortality rates were 30.8% and 36.5%, respectively, and the incidence rate of DIC was 51.9%. Compared to patients without DIC, patients with DIC showed significantly lower rates of 30-day survival (41.5% vs 96%, log-rank P < 0.001) and hospital survival (30.2% vs 86.4%, log-rank, P < 0.001). Logistic regression analyses showed that the Japanese Association for Acute Medicine (JAAM) DIC score (OR = 2.697; 95% CI, 1.408-5.169; P = 0.003) and Sequential Organ Failure Assessment (SOFA) score (OR = 1.511; 95% CI, 1.111-2.055; P = 0.009) were independent risk factors for postoperative DIC in surgical patients with NOMI. The development of postoperative DIC is a significant prognostic factor for 30-day and hospital mortalities in surgical patients with NOMI. In addition, the JAAM DIC score and SOFA score have a high discriminative ability for predicting the development of postoperative DIC.

Incidence, Outcome, and Risk Factors of Cardiovascular Surgery-Associated Disseminated Intravascular Coagulation: A Single-Center Retrospective Study.

Cardiovascular surgery is highly invasive, with a risk of postoperative coagulopathy due to various factors such as bleeding. Coagulopathy can progress to disseminated intravascular coagulation (DIC), which complicates various clinical conditions. However, no study to date has reported on DIC associated with cardiovascular surgery. Therefore, we investigated retrospectively the incidence, outcome, and risk factors of cardiovascular surgery-associated DIC in our institute. All patients who underwent cardiovascular surgery and were admitted to our intensive care unit between January 2016 and December 2017 were included in this study. The Japanese Association for Acute Medicine (JAAM) DIC score was calculated using our institute’s database at the following time points: preoperatively, postoperative day 1 (POD1), POD3, and POD7. Data regarding surgery, 90-day mortality, and risk factors of DIC were also collected and analyzed by multiple regression. In total, 553 patients were considered eligible for analysis. Median age of eligible patients was 72 years, with a 90-day mortality rate of 1.4%. Patients with DIC at POD7 had higher Sequential Organ Failure Assessment (SOFA) score, preoperative JAAM DIC scores, and a longer anesthesia time than those without DIC. Female sex, preoperative DIC score, and anesthesia time were found to be risk factors for DIC.

Early recognition of sepsis-induced coagulopathy using the C2PAC index: a ratio of soluble type C lectin-like receptor 2 (sCLEC-2) level and platelet count

C-type lectin-like receptor 2 (CLEC-2) is a platelet-activated receptor expressed on the surface of platelet membranes. Soluble CLEC-2 (sCLEC-2) has been receiving attention as a predictive marker for thrombotic predisposition. The present study examined the relationship between sCLEC-2 level and degree of coagulation disorder in septic patients. Seventy septic patients were divided into the sepsis-induced disseminated intravascular coagulation (DIC) (SID) group (n = 44) and non-SID group (n = 26). The sCLEC-2 levels were compared between the two groups. Because we suspected that the sCLEC-2 level was affected by the platelet count, we calculated the sCLEC-2/platelet count ratio (C2PAC index). We further divided septic patients into four groups using the Japanese Association for Acute Medicine (JAAM) DIC scoring system (DIC scores: 0–1, 2–3, 4–5, and 6–8). The C2PAC index was significantly higher in the SID group (2.6 ± 1.7) compared with the non-SID group (1.2 ± 0.5) (P < .001). The C2PAC indexes in the four JAAM DIC score groups were 0.9 ± 0.3, 1.1 ± 0.3, 1.7 ± 0.7, and 3.6 ± 1.0, respectively, and this index increased significantly as the DIC score increased (P < .001). According to the receiver-operating curve analysis, the area under the curve (AUC) and optimal cutoff value for the diagnosis of SID were 0.8051 and 1.4 (sensitivity, 75.0%; specificity, 76.9%), respectively. When the C2PAC index and D-dimer level, one of the main fibrinolytic markers, were selected as predictive markers for SID diagnosis in stepwise multiple logistic regression analysis, it was possible to diagnose SID with a high probability (AUC, 0.9528; sensitivity, 0.9545; specificity, 0.8846). The C2PAC index is a useful predictor of SID progression and diagnosis in septic patients.

Relationship of acute type A aortic dissection and disseminated intravascular coagulation

ObjectiveAcute type A aortic dissection (ATAAD) is a critical disease presenting with disseminated intravascular coagulation (DIC). However, the relationship between the degree of DIC and false lumen conditions remains unclear. In the present study, we evaluated the degree of preoperative DIC and the outcomes of ATAAD treatment. MethodsA total of 124 patients with ATAAD (70 men and 54 women) treated from January 2012 to January 2020 were included in the present study. The correlation between the preoperative Japanese Association for Acute Medicine (JAAM) DIC score and the false lumen diameter and length, measured using preoperative computed tomography, was examined retrospectively. The correlations were calculated using liner regression analysis. The level of statistical significance was set at P < .05. ResultsThe patients were divided into two groups: a low JAAM DIC score group and a high JAAM DIC score group. The preoperative JAAM DIC scores in the high- and low-score groups were 4.8 ± 1.2 and 1.7 ± 2.3, respectively (P < .001). The 5-year survival rates and aortic event-free rates in the low-score group were favorable compared with the high-score group; however, the differences were not statistically significant (80.8% vs 54.5%, P = .065; 63.9% vs 59.8%, P = .15, respectively). The false lumen diameter in the ascending aorta was greater in the high-score group than that in the low-score group (P < .05). The JAAM DIC score correlated significantly with the ascending false lumen diameter and the dissection length (r = 0.32 and P < .001; r = 0.29 and P = .001, respectively). A high JAAM DIC score was associated with communicating-type ATAAD (P < .05). ConclusionsOur results suggest that high preoperative JAAM DIC scores are associated with a large false lumen and communicating-type ATAAD.

Adipocytokine Profile Reveals Resistin Forming a Prognostic-Related Cytokine Network in the Acute Phase of Sepsis.

Cytokines compose a network and play crucial roles in the pathogenesis and prognosis of sepsis. Adipose tissue is an important immune endocrine organ that releases adipocytokines. This study aimed to evaluate adipocytokines in sepsis from a network perspective. This retrospective study of 37 patients with sepsis and 12 healthy controls was conducted from February 2014 to July 2015. Blood samples were collected from patients on days 1 (within 24 h of diagnosis), 2, 4, 6, 8, 11, and 15 and from healthy controls. Adipocytokines (adiponectin, leptin, resistin, chemerin, visfatin, vaspin, CXCL-12/SDF-1, angiotensinogen), inflammatory cytokines (IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12/IL-23p40, TNF-α, monocyte chemotactic protein [MCP-1]), and plasminogen activator inhibitor-1 were measured. Acute Physiology and Chronic Health Evaluation II score was evaluated on day 1, and Sequential Organ Failure Assessment (SOFA) score and Japanese Association for Acute Medicine (JAAM) and International Society of Thrombosis and Hemostasis overt disseminated intravascular coagulation (DIC) scores were assessed at the times of blood sampling. Hierarchical clustering analysis showed the cluster formed by resistin, IL-6, IL-8, MCP-1, and IL-10 on days 1, 2, and 4 represented the cytokine network throughout the acute phase of sepsis. Each cytokine in this network was significantly associated with SOFA and JAAM DIC scores over the acute phase. A Cox proportional hazards model focusing on the acute phase showed a significant relation of these five cytokines with patient prognosis. Adipocytokines and an inflammatory cytokine profile assessed over time in sepsis patients showed that resistin was involved in an inflammatory cytokine network including IL-6, IL-8, IL-10, and MCP-1 in the acute phase of sepsis, and this network was associated with severity and prognosis of sepsis.

Predicting mortality in patients with disseminated intravascular coagulation after cardiopulmonary bypass surgery by utilizing two scoring systems.

: We evaluated clinical and laboratory biomarkers of disseminated intravascular coagulation (DIC) following cardiac surgery in the cardiothoracic surgical ICU (CTICU) to predict mortality. We retrospectively analyzed CTICU patients with suspected DIC identified from the hospital laboratory database, and calculated International Society on Thrombosis and Haemostasis (ISTH) and the Japanese Association for Acute Medicine (JAAM) DIC scores to predict DIC-related mortality. The predictive accuracy of the JAAM and ISTH DIC scoring system were then assessed by logistic regression analysis and receiver operative characteristics analysis, and compared to other potential predictors of mortality (e.g., Acute Physiology and Chronic Health Evaluation II, systemic inflammatory response syndrome criteria, laboratory variables). Our study showed a 30-day mortality rate of 71% in CTICU patients with DIC. The JAAM DIC score offered the best predictive accuracy [area under the curve (AUC): 0.723, 95% % confidence interval (CI): 0.638-0.947, P = 0.021], when compared with ISTH DIC score (AUC: 0.707, 95% CI: 0.491-0.923, P = 0.066) and Acute Physiology and Chronic Health Evaluation II (AUC: 0.687, 95% CI: 0.483-0.891, P = 0.110). A JAAM DIC score at least 6 was reported in 89% of the nonsurvivors and 46% of survivors (P = 0.010), and predicted mortality [odds ratio: 9.33 (1.50-58.20)] with a 73% sensitivity and a 78% specificity. Our results also show a strong relationship between acid-base derangement and mortality. This initial evaluation of DIC-related mortality in the CTICU found the standardized JAAM DIC scoring system in combination with acid-base laboratory values were most useful to predict mortality in postcardiac surgery patients with DIC. Additional prospective studies are needed to further validate our findings.

External Validation of the Two Newly Proposed Criteria for Assessing Coagulopathy in Sepsis.

Two different criteria for evaluating coagulopathy in sepsis were recently released: sepsis-induced coagulopathy (SIC) and sepsis-associated coagulopathy (SAC). Although both use universal haemostatic markers of platelet count and pro-thrombin time, significance and usefulness of these criteria remain unclear. This article validates and evaluates the significance of SIC and SAC criteria compared with the International Society on Thrombosis and Haemostasis (ISTH) overt disseminated intravascular coagulation (DIC) and Japanese Association for Acute Medicine (JAAM) DIC criteria. Clinical characteristics of patients from a nationwide Japanese cohort were classified by SIC, SAC or DIC status and relations between criteria were examined. We evaluated associations between in-hospital mortality and anticoagulant therapy according to the SIC, SAC or DIC status to clarify the significance of criteria for introducing anticoagulants. Intervention effects were analysed by Cox regression analysis adjusted by propensity scoring. Incidences of coagulopathy diagnosed by SIC and JAAM DIC were similar, whereas those of SAC and ISTH overt DIC were about half of the former two (61.4%, 60.8% vs. 45.3%, 29.3%). Severity and mortality of all criteria were almost comparable. For validating initiation of anticoagulation, favourable effects of anticoagulant therapy were observed only in sub-sets with, and not without, coagulopathy diagnosed by all four criteria. Slight non-significant differences between anticoagulant groupings were found in ISTH overt DIC- and SAC-negative populations, suggesting that some patients even 'without' these criteria may benefit from anticoagulant therapy. Newly developed SIC diagnostic criteria for coagulopathy may be valuable in detecting appropriate candidates for anticoagulant therapy in sepsis and a useful alternative to conventional DIC scoring systems.

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

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.

Prognostic impact of disseminated intravascular coagulation score in acute heart failure patients referred to a cardiac intensive care unit: a retrospective cohort study.

Thrombosis within the vascular system in relation to inflammation and stasis is potentially associated with poor prognosis in patients with heart failure. The aim of this study was to clarify the association between disseminated intravascular coagulation (DIC) score, a scoring system for microvascular thrombosis and multiple organ dysfunction, and outcome in hospitalized patients with acute heart failure (AHF). We retrospectively evaluated 160 AHF patients referred to a cardiac intensive care unit who had their DIC score measured according to the Japanese Association for Acute Medicine (JAAM) DIC scoring system on admission. Platelet count, prothrombin time ratio, fibrin/fibrinogen degradation products, and the criteria for systemic inflammatory response syndrome were measured. Using the JAAM DIC score, the prevalence of DIC (score ≥4) in AHF patients was 5.0% (8 of 160 patients). The risk of death for patients grouped according to the DIC score was 27.8%, 46.2%, and 87.5% for DIC scores 0-1, 2-3, and ≥4, respectively (median follow-up 460 days). In multivariate analysis adjusted for various markers of disease severity, a DIC score ≥2 was independently associated with a higher all-cause death rate (adjusted hazard ratio 2.45; P = 0.005) and a higher rate of reaching the combined endpoint of all-cause death and readmission for AHF (adjusted hazard ratio 2.10; P = 0.006) after admission for AHF. In an intensive care setting, measurement of DIC score on admission could help risk stratification in hospitalized patients with AHF.

What factor within the Japanese Association for Acute Medicine (JAAM) disseminated intravascular coagulation (DIC) criteria is most strongly correlated with trauma induced DIC? A retrospective study using thromboelastometry in a single center in Japan

PurposeThe diagnostic criteria for disseminated intravascular coagulation (DIC) established by the Japanese Association for Acute Medicine (JAAM) is able to diagnose DIC accurately and promptly. The aim of this retrospective study is to evaluate the degree of association between each parameter of JAAM DIC criteria and the diagnosis of trauma induced DIC (T-DIC) utilizing thromboelastometry (ROTEM).MethodsTrauma patients transported to our hospital with ROTEM performed in the emergency department between January 2013 and December 2015 were enrolled in this study. We evaluated (1) the characteristics of T-DIC, (2) the relationships between T-DIC and each parameter of the JAAM DIC criteria and (3) the diagnostic accuracies of each parameter for T-DIC by statistical measurement.ResultsAll 72 patients (21 T-DIC and 51 control) were included in primary analysis. T-DIC was significantly related to younger age, more severe trauma scores, more cases of massive transfusions, and remarkable coagulation abnormality detected by standard coagulation tests. In the cases of T-DIC, ROTEM showed longer clotting time, lower acceleration, lower clot firmness, and inhibited fibrinolysis in EXTEM/INTEM. Within the JAAM DIC score, PT-INR ≥1.2 was the most accurate factor for T-DIC diagnosis; sensitivity 60.0%, specificity 100.0%, and accuracy 88.7%. PT-INR ≥1.2 was statistically correlated with the JAAM DIC score (p < 0.001, r = 0.709). The univariate analysis based on 1.2 of PT-INR indicated statistical differences in most categories of ROTEM, which is similar to analysis performed for the presence and absence of T-DIC.ConclusionsAmong JAAM DIC criteria, the PT-INR ≥1.2 was the most accurate factor for both the diagnosis of T-DIC and the evaluation of its severity.

Can rotational thromboelastometry predict septic disseminated intravascular coagulation?

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.

Design and Evaluation of New Unified Criteria for Disseminated Intravascular Coagulation Based on the Japanese Association for Acute Medicine Criteria

Current disseminated intravascular coagulation (DIC) criteria are insufficient for predicting mortality. Hemostatic endothelial molecular markers are useful for DIC diagnoses. We aimed to design new DIC criteria involving these markers based on the recently published Japanese Association for Acute Medicine (JAAM) DIC criteria, which exhibit higher sensitivity for mortality. Patients with severe sepsis or septic shock admitted to a tertiary referral hospital in Japan between September 2009 and November 2011 were included. Clinical data, including hemostatic endothelial molecular markers, were measured within 12 hours after admission. Receiver operating characteristic analyses were conducted for 8 candidate variables to identify the mortality-related markers. Then, we designed new unified criteria based on the JAAM DIC criteria and involving the identified optimal markers. Of the 79 patients, 66 (83.5%) survived and 13 (16.5%) died. Protein C activity correlated best with mortality with a very high prognostic value (area under the curves [AUCs] = 0.850; P < .001), followed by plasminogen activator inhibitor 1 (AUC = 0.828; P < .001). The unified criteria, consisting of the JAAM DIC criteria plus these 2 markers, exhibited greater prognostic value for mortality (sensitivity, 84.6%; specificity, 80.3%). Moreover, DIC-positive patients using the unified criteria had significantly higher disease severity, as indicated by the Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores. Our unified criteria involving hemostatic endothelial molecular markers reflected not only mortality but also the severity of illness in patients with severe sepsis.

Post-marketing surveillance data of thrombomodulin alfa: sub-analysis in patients with sepsis-induced disseminated intravascular coagulation.

BackgroundThrombomodulin alfa (TM-α, recombinant thrombomodulin) significantly improved disseminated intravascular coagulation (DIC) when compared with heparin therapy in a phase III study. Post-marketing surveillance of TM-α was performed to evaluate the effects and safety in patients with sepsis-induced DIC.MethodsFrom May 2008 to April 2010, a total of 1,787 patients with sepsis-induced DIC treated with TM-α were registered. DIC was diagnosed based on the Japanese Association for Acute Medicine (JAAM) criteria. The DIC resolution and survival rates on day 28 after the last TM-α administration, and changes in DIC, systemic inflammatory response syndrome (SIRS), and sequential organ failure assessment (SOFA) scores and coagulation and inflammation markers were evaluated.ResultsThe most frequent underlying disease was infectious focus-unknown sepsis (29.8%). The mean ± SD values of age, dose, and the duration of TM-α administration were 64.7 ± 20.3 years, 297.3 ± 111.4 U/kg/day, and 5.6 ± 3.4 days, respectively. A total of 1,320 subjects (73.9%) received combined administration with other anticoagulants. Both coagulation and inflammation markers, such as fibrin/fibrinogen degradation products, prothrombin time ratio, thrombin-antithrombin complex, and C-reactive protein, as well as JAAM DIC, SIRS, and SOFA scores, significantly and simultaneously decreased after TM-α administration (p < 0.001). DIC resolution and 28-day survival rates were 44.4% and 66.0%, respectively. The 28-day survival rate decreased significantly according to the duration of DIC before TM-α administration (p < 0.001). Total adverse drug reactions (ADRs), bleeding ADRs, and serious bleeding adverse events occurred in 126 (7.1%), 98 (5.5%), and 121 (6.8%) subjects, respectively. On day 28, after the last TM-α administration available for an antibody test, only one patient was positive for anti-TM-α antibodies (0.11%).ConclusionOur results suggest that TM-α is most effective for treating patients with sepsis-induced DIC when administered within the first 3 days after diagnosis.

A multicenter, prospective validation study of the Japanese Association for Acute Medicine disseminated intravascular coagulation scoring system in patients with severe sepsis

IntroductionTo validate the Japanese Association for Acute Medicine (JAAM) disseminated intravascular coagulation (DIC) scoring system in patients with severe sepsis, we conducted a multicenter, prospective study at 15 critical care centers in tertiary care hospitals.MethodsThis study included 624 severe sepsis patients. JAAM DIC was scored on the day of diagnosis of severe sepsis (day 1) and day 4. Scores for disease severity and organ dysfunction were also evaluated.ResultsThe prevalence of JAAM DIC was 46.8% (292/624), and 21% of the DIC patients were scored according to the reduction rate of platelets. The JAAM DIC patients were more seriously ill and exhibited more severe systemic inflammation, a higher prevalence of multiple organ dysfunction syndrome (MODS) and worse outcomes than the non-DIC patients. Disease severity, systemic inflammation, MODS and the mortality rate worsened in accordance with an increased JAAM DIC score on day 1. The Kaplan-Meier curves demonstrated lower 1-year survival in the JAAM DIC patients than in those without DIC (log-rank test P <0.001). The JAAM DIC score on day 1 (odds ratio = 1.282, P <0.001) and the Delta JAAM DIC score (odds ratio = 0.770, P <0.001) were independent predictors of 28-day death. Dynamic changes in the JAAM DIC score from days 1 to 4 also affected prognoses. The JAAM DIC scoring system included all patients who met the International Society on Thrombosis and Haemostasis overt DIC criteria on day 1. The International Society on Thrombosis and Haemostasis scoring system missed a large number of nonsurvivors recognized by the JAAM scoring system.ConclusionsThe JAAM DIC scoring system exhibits good prognostic value in predicting MODS and poor prognosis in patients with severe sepsis and can detect more patients requiring treatment. Conducting repeated daily JAAM scoring increases the ability to predict the patient's prognosis.

A low TAFI activity and insufficient activation of fibrinolysis by both plasmin and neutrophil elastase promote organ dysfunction in disseminated intravascular coagulation associated with sepsis

IntroductionWe hypothesized that thrombin activatable fibrinolysis inhibitor (TAFI) and the activation of fibrinolysis by both plasmin and neutrophil elastase is insufficient to overcome fibrinolytic shutdown, contributing to multiple organ dysfunction syndrome (MODS) in sepsis-induced disseminated intravascular coagulation (DIC). Materials and MethodsFifty patients with sepsis were prospectively enrolled. The DIC was diagnosed based on the Japanese Association for Acute Medicine (JAAM) DIC and the International Society on Thrombosis and Haemostasis (ISTH) overt DIC criteria. ResultsThe JAAM DIC scores were independent predictors of patient death and MODS. The JAAM DIC patients, especially those who met the ISTH overt DIC criteria, showed lower TAFI activity, and higher levels of soluble fibrin, neutrophil elastase, fibrin degradation product by neutrophil elastase (EXDP), plasmin-alpha2 plasmin inhibitor complex (PPIC), tissue plasminogen activator-plasminogen activator inhibitor-1 complex (tPAIC) and D-dimer in comparison with non-DIC patients. There were differences in the levels of soluble fibrin, tPAIC, TAFI activity, and neutrophil elastase between the patients with and without MODS. However, no differences were observed in the levels of PPIC, D-dimer, or EXDP. Soluble fibrin negatively correlated with the TAFI activity. High neutrophil elastase, low TAFI activity and PPIC are independent predictors of patient death and MODS. tPAIC is an independent predictor of elevation of EXDP in DIC patients. ConclusionsActivation of fibrinolysis both by plasmin and neutrophil elastase cannot overcome fibrinolytic shutdown, leading to MODS and a poor outcome in sepsis-induced DIC. The systemic activation of neutrophils and a low TAFI activity are also involved in the pathogenesis of MODS.

Prospective comparison of new Japanese Association for Acute Medicine (JAAM) DIC and International Society of Thrombosis and Hemostasis (ISTH) DIC score in critically ill septic patients

IntroductionWe prospectively compared the new Japanese Association for Acute Medicine (JAAM) score with the International Society of Thrombosis and Hemostasis (ISTH) score for diagnosis of disseminated intravascular coagulation (DIC) in septic patients admitted in a general critical care intensive care unit. Material and methodSeptic patients with platelet count of <150×109/L were included. Both DIC scores were estimated from day 1 to day 4 along with APACHE II and SOFA scores. ResultsOut of the 148 blood samples drawn from 42 patients (28 male & 14 female) the JAAM and ISTH DIC scores had an overall significant agreement (k=0.246, p<0.001) in 83 samples. JAAM score had higher diagnostic rates on all four days. Significant (p≤0.001) day wise variation existed in JAAM and ISTH DIC scores. Correlation between JAAM DIC and ISTH DIC scores on day 1 (r=0.631) & day 4 (r=0.609) was significant (p<0.001). Pneumonia was the predominant cause of sepsis. Twenty seven (64.3%) patients died during their stay in ICU. Amongst DIC patients both severity scores (SOFA/APACHE II) and DIC scores (JAAM/ISTH) did not discriminate between survivors and non-survivors. Health care associated infection (p=0.040), high lactate levels (p=0.020) on day 1 and high procalcitonin levels (p=0.036) were found to have significant discriminating ability between survivors and non-survivors. Significantly shorter length of stay was observed amongst non-survivors (p=0.002). ConclusionsIn sepsis the JAAM DIC score identified most of the patients diagnosed by the overt ISTH criteria, but failed to discriminate between survivors and non-survivors amongst DIC patients.

Prospective external validation of the new scoring system for disseminated intravascular coagulation by Japanese Association for Acute Medicine (JAAM)

Introduction A new disseminated intravascular coagulation (DIC) scoring system was recently announced by Japanese Association for Acute Medicine (JAAM). We have conducted a prospective external validation study to assess the accuracy of this scoring system. Materials and methods All patients admitted to the ICU in a tertiary academic hospital in 2007 were prospectively observed. All patients younger than 15 years of age, those who stayed in the ICU for less than 24 hours, had cardiac surgery, hematological diseases, recent chemotherapy or radiotherapy or liver cirrhosis were excluded. The remaining patients were then screened using the JAAM DIC scoring system. Results DIC was diagnosed by the JAAM DIC scoring system in 45 of the 242 patients screened (18.6%). The DIC patients were older, had a higher Acute Physiology and Chronic Health Evaluation (APACHE) II score and stayed in the ICU longer in comparison to the non-DIC patients. However, hospital mortality was similar between the two groups (p = 0.98). There was no difference in the JAAM DIC score between the surviving and non-surviving DIC patients (p = 0.40). A multivariate logistic regression analysis revealed the DIC diagnosed by JAAM to have a non-significant low odds ratio for hospital mortality (OR 0.29, 95% CI 0.08-1.08, p = 0.066). Conclusion We have reported an external validation study of the JAAM DIC scoring system, which was conducted outside of the centers where data for developing the score were collected. DIC diagnosed by this scoring system was not related to hospital mortality.

Disseminated intravascular coagulation with a fibrinolytic phenotype at an early phase of trauma predicts mortality

Introduction Disseminated intravascular coagulation (DIC) with an antifibrinolytic phenotype is characterized by microvascular thrombosis leading to poor outcome at the late-stage of trauma. To test the hypothesis that DIC with a fibrinolytic phenotype at an early stage of trauma also contributes to a poor outcome due to severe bleeding, we conducted a retrospective, cohort study. Materials and Methods The subjects included 314 consecutive severe trauma patients. A systematic review of medical records of the patients was conducted to provide the base line characteristics and DIC-related variables. The data of these variables were obtained at 4 time points within 24 hr after arrival to the emergency department (ED); Time Point 1, immediately after arrival to the ED to 4 hr after arrival; Time Point 2, 4 to 8 hr after arrival; Time Point 3, 8 to 16 hr after arrival; Time Point 4, 16 to 24 hr after arrival. Results Nonsurvivors (87.3%, 48/55) met the Japanese Association for Acute Medicine (JAAM) DIC criteria showing lower fibrinogen levels, a prolonged prothrombin time, and higher fibrin/fibrinogen degradation products (FDP) and D-dimer levels in comparison to those of the 289 survivors. The FDP/D-dimer ratio and lactate level were significantly higher in the nonsurvivors than those of the survivors. Lower fibrinogen levels and higher FDP/D-dimer ratio suggest fibrinogenolysis in DIC of the nonsurvivors. Furthermore a stepwise logistic regression analysis showed that the JAAM DIC score, levels of fibrinogen, FDP and lactate at Time Point 1 are independent predictors of death. Low levels of fibrinogen and high FDP but not D-dimer predict massive bleeding at an early stage of trauma. The optimal cutoff points for the prediction of death and massive bleeding were fibrinogen (1.90, 1.90 g/L) and FDP (35.2, 68.7 mg/L), respectively. Conclusions DIC with a fibrinolytic phenotype modified through fibrinogenolysis at an early phase of trauma contributes to poor prognosis due to massive bleeding. Tissue hypoperfusion may be involved in the pathogenesis of this type of DIC.