不同DIC诊断评分标准对严重脓毒症患者病情评价的比较

目的:探讨不同DIC评分标准判断严重脓毒症和脓毒症休克的患者DIC和MODS发生和预后的价值。方法:收集246例严重脓毒症和脓毒症休克患者入院第1、3、7天的各项生理参数和实验室指标,分别使用ISTH显性DIC评分标准、非显性DIC评分标准和JAAMDIC评分标准进行诊断评分,同时进行SOFA评分,观察不同DIC评分标准之间确诊率、诊断时间点的差异;比较DIC确诊组间的病死率、SOFA分值的差异,绘制三种DIC评分标准的ROC曲线,计算曲线下面积,衡量各个评分系统对危重患者的病情严重程度和预后的判断准确性。结果:三种评分标准均能在一定程度上准确反映危重病患者多脏器功能衰竭的发生和预后,使用ISTH显性标准确诊的患者病死率和SOFA分值最高,诊断时间点同时或晚于ISTH非显性标准和JAAM标准;在DIC确诊组间的病死率和SOFA分值的比较上,JAAM标准与ISTH显性标准之间差异无统计学意义(P>0.05),ISTH非显性标准与ISTH显性标准之间差异有统计学意义,JAAM标准和ISTH非显性标准之间,病死率差异无统计学意义、SOFA分值差异有统计学意义;3个评分标准的ROC曲线下面积分别为0.739、0.724和0.778,相互之间比较差异均有统计学意义。结论:ISTH显性标准诊断DIC特异性最高,敏感性差;ISTH非显性标准诊断DIC敏感性最高,特异性差;JAAM标准诊断DIC敏感性和特异性均较高,对危重病患者的MODS发生和预后判断更为准确,可作为早期干预治疗的首选诊断标准。     

弥散性血管内凝血诊断评分标准在产科的应用评价

目的 采用已有的4种国际非孕弥散性血管内凝血（DIC）诊断评分标准对产科DIC的诊断进行评估，探索更适合产科DIC诊断的“金标准”。 方法 选择2009年6月－2012年6月期间产科拟诊DIC的孕产妇为研究对象，用日本卫生福利部（JMHW）提出的JMHW、日本危重病协会（JAAM）提出的JAAM、国际血栓与止血委员会（ISTH）提出的ISTH显性和ISTH非显性4种诊断评分标准联合诊断和构建“金标准”，以此评价4种诊断标准对产科DIC诊断的特性。 结果 受试者工作特征（ROC）曲线分析显示ISTH非显性标准、ISTH显性标准、JMHW、JAAM的ROC曲线下面积分别为0.939、0.865、0.867、0.867，ISTH非显性标准灵敏度和特异度与“金标准”在不同诊断界值时较一致，同时优于其他3种诊断标准。 结论 ISTH非显性标准较适合作为临床产科DIC诊断，其对产科这一特殊发病人群的DIC诊断具有更科学的临床诊断价值。     

SIRS-associated coagulopathy and organ dysfunction in critically ill patients with thrombocytopenia

BACKGROUNDS: Coagulopathy and thrombocytopenia often occur in critically ill patients, and disseminated intravascular coagulation (DIC) can lead to multiple organ dysfunction and a poor outcome. However, the relation between coagulopathy and systemic inflammatory response has not been thoroughly clarified. Thus, we evaluated coagulative activity, organ dysfunction, and systemic inflammatory response syndrome (SIRS) in critically ill patients with thrombocytopenia and examined the balance between coagulopathy and systemic inflammation. PATIENTS AND METHODS: Two hundred seventy-three patients, who were admitted to 13 critical care centers in Japan and fulfilled the criteria of platelet count of less than 150*10(9)/L, were included. Coagulative variables (platelet count, fibrin/fibrinogen degradation products, and DIC scores), organ dysfunction index (Sequential Organ Failure Assessment [SOFA] score), and SIRS score in each patient were evaluated for 4 consecutive days after fulfilling the above entry criteria. The effect of SIRS on coagulopathy and organ dysfunction was evaluated in these patients. RESULTS: Both the maximum SIRS score and entry SIRS score had significant relation to the maximum SOFA score during the observation period. Coagulation disorders indicated by the minimum platelet count, maximum DIC scores, and positivity for DIC worsened gradually with increases in SIRS scores. Both the minimum platelet count and maximum DIC scores were significantly correlated with the maximum SOFA score, indicating that a relation exists between coagulopathy and organ dysfunction. CONCLUSIONS: In critically ill patients with thrombocytopenia, coagulopathy and organ dysfunction progress with significant mutual correlation, depending on the increase in SIRS scores. The SIRS-associated coagulopathy may play a critical role in inducing organ dysfunction after severe insult.     

Using angiogenic factors and their soluble receptors to predict organ dysfunction in patients with disseminated intravascular coagulation associated with severe trauma

ABSTRACT: INTRODUCTION: Disseminated intravascular coagulation (DIC) is characterized by the concomitant activation of coagulofibrinolytic disorders and systemic inflammation associated with endothelial dysfunction-induced microvascular permeability. Angiogenic factors, including vascular endothelial growth factor (VEGF), angiopoietin (Ang), and their receptors, play crucial roles in angiogenesis and microvascular permeability. The aim of the study was to assess the relationship between angiogenic factors, their soluble receptors and organ dysfunction associated with DIC after severe trauma. MATERIALS AND METHODS: A total of 57 patients with severe trauma were divided into two subgroups; 30 DIC patients and 27 non-DIC patients. 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. The serum levels of angiogenic factors were measured at the time of admission (Day 1), Day 3 and Day 5. This study compared levels of these angiogenic factors between the two DIC groups, and evaluated their predictive value for organ dysfunction. RESULTS: DIC patients, especially those with ISTH DIC, showed higher Sequential Organ Failure Assessment (SOFA) scores and lactate levels. There were lower levels of VEGF, Ang1 and the soluble Tie2 in the ISTH DIC patients than the non-DIC patients. The levels of soluble VEGF receptor-1 (sVEGFR1), Ang2 and the Ang2/Ang1 ratio in the ISTH DIC patients were higher than in non-DIC patients. The relationship between the presence of massive transfusion and angiogenic factors indicated the same results. The levels of sVEGFR1, Ang2 and the Ang2/Ang1 ratio correlated with the SOFA scores. In particular, sVEGFR1 and Ang2 were independent predictors of an increase in the SOFA score. The lactate levels independently predicted increases in the levels of sVEGFR1 and Ang2. The decrease in the platelet counts also independently predicted the increase in Ang2 levels in DIC patients. CONCLUSIONS: Angiogenic factors and their soluble receptors, particularly sVEGFR1 and Ang2, are considered to play pivotal roles in the development of organ dysfunction in DIC associated with severe trauma. DIC-induced tissue hypoxia and platelet consumption may play crucial roles in inducing sVEGFR1 and Ang2, and in determining the prognosis of the severity of organ dysfunction.     

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

Introduction

To 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.

Methods

This 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.

Results

The 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.

Conclusions

The 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.     

Modified score for disseminated intravascular coagulation in the critically ill

Objective To assess the value of the diagnosis of overt disseminated intravascular coagulation (DIC) according to the International Society on Thrombosis and Haemostasis (ISTH) criteria and that of the parameters included in the ISTH score for overt DIC in predicting day 28 mortality in intensive care patients. Also, to assess the value of the components of the score in the diagnosis of overt DIC.Design and setting Retrospective clinical study in a university hospital intensive care unit.Patients and participants 494 consecutive patients admitted in the ICU between January 2002 and October 2003.Measurements and results Clinical and laboratory data, including hemostatic parameters, were collected from computerized databases and patient files. Altogether 19% (95/494) of the patients fulfilled the criteria for overt DIC. Their day 28 mortality rate was higher than that of patients without overt DIC (40% vs. 16%). The lowest platelet count (area under curve, AUC, 0.910), highest plasma D-dimer (AUC 0.846), lowest antithrombin (AUC 0.823), and Owren-type prothrombin time activity (AUC 0.797) discriminated well the patients with and without overt DIC, whereas plasma fibrinogen (AUC 0.690) had poor discriminative power. No patient with the diagnosis of overt DIC had decreased plasma fibrinogen. Day-1 SOFA and APACHE II score, the first CRP measurement, and the lowest antithrombin were independent predictors of day 28 mortality.Conclusions The diagnosis of overt DIC was not an independent predictor of day 28 mortality. In ICU patients plasma antithrombin seems a promising candidate in the panel of indicators for overt DIC whereas the value of plasma fibrinogen is in doubt.     

Treatment effects of drotrecogin alfa (activated) in patients with severe sepsis with or without overt disseminated intravascular coagulation.

Disseminated intravascular coagulation (DIC) is a serious condition associated with sepsis. Clinical management of DIC is hampered by lack of clear diagnostic criteria. The International Society on Thrombosis and Haemostasis (ISTH) has proposed a diagnostic scoring algorithm for overt DIC based on routine laboratory tests. The objective was to assess a modified version of the ISTH scoring system and determine the effect of drotrecogin alfa (activated) (DrotAA, recombinant human activated protein C) on patients with DIC. The large database from the PROWESS clinical trial in severe sepsis was retrospectively used to assess a modified ISTH scoring system. Baseline characteristics and treatment effects of DrotAA were evaluated. At baseline, 29% (454/1568) of patients had overt DIC. Overt DIC was a strong predictor of mortality, independent of APACHE II score and age. Placebo-treated patients with overt DIC had higher mortality than patients without (43 vs. 27%). DrotAA-treated patients with overt DIC had a trend towards greater relative risk reduction in mortality than patients without (29 vs. 18%, P = 0.261) but both groups had greater relative risk reduction than placebo-treated patients. Serious bleeding rates during DrotAA infusion in patients with and without overt DIC were slightly increased (P = 0.498), compared with placebo, while clinically overt thrombotic events during the 28-day period were slightly reduced (P = 0.144). Modified ISTH overt DIC scoring may be useful as an independent assessment for identifying severe sepsis patients at high risk of death with a favorable risk/benefit profile for DrotAA treatment. Patients without overt DIC also received significant treatment benefit.     

中性粒细胞胞外诱捕网标志物游离DNA水平与脓毒症血小板活化的相关性

目的研究中性粒细胞胞外诱捕网（NETs）标志物游离DNA（cfDNA）水平与血小板（PLT）活化之间的相关性。 方法根据纳入标准、排除标准将2018年9至12月中国医科大学附属第一医院ICU收治的51例患者分为脓毒症组（29例）和对照组（22例）。用酶联免疫吸附测定（ELISA）方法检测患者外周血浆的cfDNA、血小板因子4（PF4）、P-选择素浓度。采用SPSS 25.0进行统计学分析，比较2组患者入ICU 24 h内生化指标、急性生理学与慢性健康状况（APACHEⅡ）评分、序贯器官衰竭评估（SOFA）评分、国际血栓与止血委员会（ISTH）评分、日本危重病协会（JAAM）评分、cfDNA以及PLT标志物（PF4、P-选择素）的差异性。同时将脓毒症组cfDNA和PLT、PLT标志物（PF4、P-选择素）、炎症指标［中性粒细胞计数（NE）、C反应蛋白（CRP）、降钙素原（PCT）］、凝血指标［凝血酶原时间（PT）、活化部分凝血酶时间（APTT）、D-二聚体（D-D）、抗凝血酶Ⅲ活性（AT-Ⅲ）］、疾病严重程度（APACHEⅡ评分、SOFA评分、ISTH评分、JAAM评分）等分别进行相关性分析。 结果脓毒症组患者cfDNA水平明显高于对照组，差异有统计学意义［（174.499±76.596）ng/ml vs （114.354±19.319）ng/ml，P＜0.05］，但2组P-选择素、PF4水平比较，差异无统计学意义（P＞0.05）。脓毒症组中cfDNA水平与P-选择素/PLT、D-D、CRP、APACHEⅡ评分、JAAM评分之间具有相关性（r=0.3849、0.3872、0.6211、0.4542、0.4451，P＜0.05）；与NE、PLT计数、PLT标志物（PF4、P-选择素）、ISTH评分等无明显相关性（P＞0.05）。 结论脓毒症组患者cfDNA明显升高。脓毒症组中cfDNA与D-D之间具有明显正相关性，提示NETs可能与继发性纤溶过程关系更加密切。尽管脓毒症组中cfDNA与P-选择素/PLT之间有正相关性，但因为P-选择素并不是特异性的PLT活化标志物，所以NETs与脓毒症PLT活化的关系仍需进一步探究。     

A randomized,controlled, multicenter trial of the effects of antithrombin on disseminated intravascular coagulation in patients with sepsis

Introduction

To test the hypothesis that the administration of antithrombin concentrate improves disseminated intravascular coagulation (DIC), resulting in recovery from DIC and better outcomes in patients with sepsis, we conducted a prospective, randomized controlled multicenter trial at 13 critical care centers in tertiary care hospitals.

Methods

We enrolled 60 DIC patients with sepsis and antithrombin levels of 50 to 80% in this study. The participating patients were randomly assigned to an antithrombin arm receiving antithrombin at a dose of 30 IU/kg per day for three days or a control arm treated with no intervention. The primary efficacy end point was recovery from DIC on day 3. The analysis was conducted with an intention-to-treat approach. DIC was diagnosed according to the Japanese Association for Acute Medicine (JAAM) scoring system. The systemic inflammatory response syndrome (SIRS) score, platelet count and global markers of coagulation and fibrinolysis were measured on day 0 and day 3.

Results

Antithrombin treatment resulted in significantly decreased DIC scores and better recovery rates from DIC compared with those observed in the control group on day 3. The incidence of minor bleeding complications did not increase, and no major bleeding related to antithrombin treatment was observed. The platelet count significantly increased; however, antithrombin did not influence the sequential organ failure assessment (SOFA) score or markers of coagulation and fibrinolysis on day 3.

Conclusions

Moderate doses of antithrombin improve DIC scores, thereby increasing the recovery rate from DIC without any risk of bleeding in DIC patients with sepsis.

Trial registration

UMIN Clinical Trials Registry (UMIN-CTR) UMIN000000882     

An observational cohort study of the performance of the REDS score compared to the SIRS criteria,NEWS2, CURB65, SOFA,MEDS and PIRO scores to risk-stratify emergency department suspected sepsis

ObjectiveTo compare the performance of the Risk-stratification of Emergency Department suspected Sepsis (REDS) score to the SIRS criteria, NEWS2, CURB65, SOFA, MEDS and PIRO scores, to risk-stratify Emergency Department (ED) suspected sepsis patients for mortality.MethodA retrospective observational cohort study of prospectively collected data. Adult patients admitted from the ED after receiving intravenous antibiotics for suspected sepsis in the year 2020, were studied. Patients with COVID-19 were excluded. The scores stated above were calculated for each patient. Receiver operator characteristics (ROC) curves were constructed for each score for the primary outcome measure, all-cause in-hospital mortality. The area under the ROC (AUROC) curves and cut-off points were identified by the statistical software. Scores above the cut-off point were deemed high-risk. The test characteristics of the high-risk groups were calculated. Comparisons were based on the AUROC curve and sensitivity for mortality of the high-risk groups. Previously published cut-off points were also studied. Calibration was also studied.ResultsOf the 2594 patients studied, 332 (12.8%) died. The AUROC curve for the REDS score 0.73 (95% confidence interval [CI] 0.72–0.75) was significantly greater than the AUROC curve for the SIRS criteria 0.51 (95% CI 0.49–0.53), p < .0001 and the NEWS2 score 0.69 (95% CI 0.67–0.70), p = .005, and similar to all other scores studied. Sensitivity for mortality at the respective cut-off points identified (REDS ≥3, NEWS2 ≥ 8, CURB65 ≥ 3, SOFA ≥3, MEDS ≥10 and PIRO ≥10) was greatest for the REDS score at 80.1% (95% CI 75.4–84.3) and significantly greater than the other scores. The sensitivity for mortality for an increase of two points from baseline in the SOFA score was 63% (95% CI 57.5–68.2).ConclusionsIn this single centre study, the REDS score had either a greater AUROC curve or sensitivity for mortality compared to the comparator scores, at the respective cut-off points identified.

KEY MESSAGES

• The REDS score is a simple and objective scoring system to risk-stratify for mortality in emergency department (MED) patients with suspected sepsis.
• The REDS score is better or equivalent to existing scoring systems in its discrimination for mortality.

     

血清降钙素原和常用炎症指标结合SOFA评分对脓毒症早期诊断和预后价值的评价

目的 结合感染相关器官功能衰竭评分(SOFA)评价血清降钙素原(PCT)和临床常用炎症指标对脓毒症的早期诊断和预后价值.方法 采用前瞻性、临床病例观察及诊断试验研究.根据美国胸科医师协会/危重病医学会(ACCP/SCCM)共识会议,严格将入选病例分为全身炎症反应综合征(SIRS)组、脓毒症组、严重脓毒症组、脓毒性休克组、非SIRS对照组.测定24 h内的炎症指标、SOFA评分及PCT浓度并进行相关分析.结果 208例患者入选,其中对照组59例,SIRS组57例,脓毒症组52例,严重脓毒症组28例,脓毒性休克组12例.血清PCT浓度与脓毒症严重程度呈正相关,Spearman相关系数为0.909(P=0.000).根据受试者工作特征曲线(ROC曲线)分析,PCT的ROC曲线下面积(AUC)为0.936±0.020,SOFA评分的AUC为0.973±0.011(P均=0.000).判断最佳诊断界值PCT为＞0.375 μg/L,SOFA评分为＞3.5分,其约登(Youden)指数分别为0.808和0.801.二分类Logistic回归分析显示,在排除了年龄、CRP混杂因素后PCT和SOFA评分与脓毒症发病明显相关,相对危险度(OR值)分别为84.794和10.761(P均=0.000),并且可以预测脓毒症的发病概率.SOFA评分是脓毒症疾病预后的最显著因子,OR值为2.084(P=0.000 2).结论 传统炎症指标和C-反应蛋白(CRP)是鉴别SIRS和非SIRS的有用指标,但不是早期诊断脓毒症的可靠指标.PCT是早期诊断脓毒症并能与SIRS鉴别的特异性较高的炎症指标;结合SOFA评分和PCT可以预测脓度症的发病概率;根据PCT值的变化,再结合SOFA评分可以客观判断脓毒症病情的严重性.SOFA评分与脓毒症预后明显相关.     

Prospective validation of the International Society of Thrombosis and Haemostasis scoring system for disseminated intravascular coagulation

OBJECTIVES: A diagnosis of disseminated intravascular coagulation (DIC) is hampered by the lack of an accurate diagnostic test. Based on the retrospective analysis of studies in patients with DIC, a scoring system (0-8 points) using simple and readily available routine laboratory tests has been proposed. The aim of this study was to prospectively validate this scoring system and assess its feasibility, sensitivity, and specificity in a consecutive series of intensive care patients. DESIGN: Prospective cohort of intensive care patients. SETTING: Adult intensive care unit in a tertiary academic center. PATIENTS: Consecutive patients with a clinical suspicion of disseminated intravascular coagulation. INTERVENTIONS: Patients were followed during their admission to the intensive care unit, and the DIC score was calculated every 48 hrs and compared with a "gold standard" based on expert opinion. In addition, an activated partial thromboplastin time (aPTT) waveform analysis, which has been reported to be a good predictor for the absence or presence of DIC, was performed. MEASUREMENTS AND MAIN RESULTS: We analyzed 660 samples from 217 consecutive patients. The prevalence of DIC was 34%. There was a strong correlation between an increasing DIC score and 28-day mortality (for each 1-point increment in the DIC score, the odds ratio for mortality was 1.25). The sensitivity of the DIC score was 91% and the specificity 97%. An abnormal aPTT waveform was seen in 32% of patients and correlated well with the presence of DIC (sensitivity 88%, specificity 97%). In 19% of patients, the aPTT waveform-based diagnosis of DIC preceded the diagnosis based on the scoring system. CONCLUSIONS: A diagnosis of DIC based on a simple scoring system, using widely available routine coagulation tests, is sufficiently accurate to make or reject a diagnosis of DIC in intensive care patients with a clinical suspicion of this condition. An aPTT waveform analysis is an interesting and promising tool to assist in the diagnostic management of DIC.     

New disseminated intravascular coagulation score: A useful tool to predict mortality in comparison with Acute Physiology and Chronic Health Evaluation II and Logistic Organ Dysfunction scores

OBJECTIVE: To compare the performance of a coagulation score-the new scoring system for diagnosing disseminated intravascular coagulation (DIC)-with the Acute Physiology and Chronic Health Evaluation (APACHE) II and Logistic Organ Dysfunction score in mortality prediction. DESIGN: Single-center retrospective study. SETTING: Medical intensive care unit of the University of Munich. PATIENTS: A total of 797 patients admitted to the intensive care unit between January 1, 1996, and January 1, 2001. METHODS: A retrospective analysis of all patients was done if the coagulation variables d-dimer, platelet count, fibrinogen, and prothrombin index were available within the first 12 hrs after admission. Patients with missing values, fibrinolytic therapy, or unknown survival status were excluded from analysis. As a marker of fibrin generation, d-dimer was measured and integrated into the scoring system for DIC together with prothrombin time, fibrinogen, and platelet count. A coagulation score was calculated in analogy with the scoring system for DIC in patients not typically developing DIC. MEASUREMENTS AND RESULTS: Overall, the mean result of the scoring system for DIC was 2.2 points. An increasing scoring system for DIC was associated with increasing mortality in patients with serious infections. Use of the scoring system for DIC in addition to the APACHE II score helps to predict mortality better than the APACHE II score alone, especially in patients with infections. The Cox regression analysis showed that the DIC and APACHE II scores correlated independently with survival time with a greater effect of the DIC score than the APACHE II or the Logistic Organ Dysfunction score. Similar results were obtained using the coagulation score in patients with cardiocirculatory diseases. CONCLUSION: Our retrospective data suggest that a combination of the APACHE II score and the scoring system for DIC predicts mortality in critically ill patients with available variables better than the APACHE II score alone. This effect is most pronounced among patients with active infection. These results of our retrospective analysis have to be confirmed in a prospective study.     

Calibration and discrimination by daily Logistic Organ Dysfunction scoring comparatively with daily Sequential Organ Failure Assessment scoring for predicting hospital mortality in critically ill patients

OBJECTIVE: The Logistic Organ Dysfunction (LOD) score has been proved effective in evaluating severity during the first day in an intensive care unit but has not been evaluated later. To evaluate attributable mortality related to nosocomial events, organ dysfunction scores that remain accurate throughout the intensive care unit stay are needed. The objective of this study was to evaluate how accurately daily LOD scoring predicts mortality comparatively with daily Sequential Organ Failure Assessment (SOFA) scoring. DESIGN: Prospective multicenter study. SETTING: Six intensive care units in France. PATIENTS: A total of 1685 patients with intensive care unit stays longer than 48 hrs were included in this study (511 hospital deaths). Median age was 66 yrs, and median Simplified Acute Physiology Score II at admission was 38. For each patient, a senior physician recorded the variables needed to compute organ dysfunction scores daily throughout the intensive care unit stay. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: SOFA and LOD scores were computed daily during the first 7 days. Calibration was evaluated based on goodness-of-fit by the Hosmer-Lemeshow chi-square statistic (lower chi-square values and higher values indicate better fit) and discrimination based on the receiver operating characteristics (ROC) area under the curve (AUC; a ROC-AUC of 1 indicates faultless discrimination and a ROC-AUC of 0.5 indicates the effects of chance alone). Because calibration of both scores was poor at all time points ( p<.001), customization was performed using the total score (model 1) or separate introduction of each dysfunction (model 2). The performance of customized LOD and SOFA scores on a given day in predicting mortality was assessed in those patients who spent at least one more calendar day in the intensive care unit. The original LOD and SOFA scores had satisfactory ROC-AUC values (0.720 to 0.766). Internal consistency of both scores was acceptable ( p< 10(-4) for each organ dysfunction). After customization, the original scores calibrated well between days 1 and 7. Discrimination by both scores was better with model 2 (AUC-ROC, 0.729-0.784). CONCLUSION: Daily LOD and SOFA scores showed good accuracy and internal consistency, and they could be used to adjust severity for events occurring in the intensive care unit.     

Treatment effects of high-dose antithrombin without concomitant heparin in patients with severe sepsis with or without disseminated intravascular coagulation

BACKGROUND: Disseminated intravascular coagulation (DIC) is a serious complication of sepsis that is associated with a high mortality. OBJECTIVES: Using the adapted International Society on Thrombosis and Haemostasis (ISTH) diagnostic scoring algorithm for DIC, we evaluated the treatment effects of high-dose antithrombin (AT) in patients with severe sepsis with or without DIC. PATIENTS AND METHODS: From the phase III clinical trial in severe sepsis (KyberSept), 563 patients were identified (placebo, 277; AT, 286) who did not receive concomitant heparin and had sufficient data for DIC determination. RESULTS: At baseline, 40.7% of patients (229 of 563) had DIC. DIC in the placebo-treated patients was associated with an excess risk of mortality (28-day mortality: 40.0% vs. 22.2%, P < 0.01). AT-treated patients with DIC had an absolute reduction in 28-day mortality of 14.6% compared with placebo (P = 0.02) whereas in patients without DIC no effect on 28-day mortality was seen (0.1% reduction in mortality; P = 1.0). Bleeding complications in AT-treated patients with and without DIC were higher compared with placebo (major bleeding rates: 7.0% vs. 5.2% for patients with DIC, P = 0.6; 9.8% vs. 3.1% for patients without DIC, P = 0.02). CONCLUSIONS: High-dose AT without concomitant heparin in septic patients with DIC may result in a significant mortality reduction. The adapted ISTH DIC score may identify patients with severe sepsis who potentially benefit from high-dose AT treatment.     

Hemostasis during the early stages of trauma: comparison with disseminated intravascular coagulation

Introduction

We tested two hypotheses that disseminated intravascular coagulation (DIC) and acute coagulopathy of trauma-shock (ACOTS) in the early phase of trauma are similar disease entities and that the DIC score on admission can be used to predict the prognosis of patients with coagulopathy of trauma.

Methods

We conducted a retrospective study of 562 trauma patients, including 338 patients whose data were obtained immediately after admission to the emergency department. We collected serial data for the platelet counts, global markers of coagulation and fibrinolysis, and antithrombin levels. DIC was diagnosed according to the Japanese Association for Acute Medicine (JAAM) DIC scoring system, and ACOTS was defined as a prothrombin-time ratio of >1.2.

Results

The higher levels of fibrin/fibrinogen degradation products (FDP) and D-dimer and greater FDP/D-dimer ratios in the DIC patients suggested DIC with the fibrinolytic phenotype. The DIC patients with the fibrinolytic phenotype exhibited persistently lower platelet counts and fibrinogen levels, increased prothrombin time ratios, higher FDP and D-dimer levels, and lower antithrombin levels compared with the non-DIC patients on arrival to the emergency department and during the early stage of trauma. Almost all ACOTS patients met the criteria for a diagnosis of DIC; therefore, the same changes were observed in the platelet counts, global markers of coagulation and fibrinolysis, and antithrombin levels as noted in the DIC patients. The JAAM DIC score obtained immediately after arrival to the emergency department was an independent predictor of massive transfusion and death due to trauma and correlated with the amount of blood transfused.

Conclusions

Patients who develop DIC with the fibrinolytic phenotype during the early stage of trauma exhibit consumption coagulopathy associated with increased fibrin(ogen)olysis and lower levels of antithrombin. The same is true in patients with ACOTS. The JAAM DIC score can be used to predict the prognosis of patients with coagulopathy of trauma.     

Reliability and accuracy of Sequential Organ Failure Assessment (SOFA) scoring

OBJECTIVE: The Sequential Organ Failure Assessment (SOFA) score was developed to quantify the severity of patients' illness, based on the degree of organ dysfunction. This study aimed to evaluate the accuracy and the reliability of SOFA scoring. DESIGN: Prospective study. SETTING: Adult intensive care unit (ICU) in a tertiary academic center. SUBJECTS: Thirty randomly selected patient cases and 20 ICU physicians. MEASUREMENTS AND MAIN RESULTS: Each physician scored 15 patient cases. The intraclass correlation coefficient was .889 for the total SOFA score. The weighted kappa values were moderate (0.552) for the central nervous system, good (0.634) for the respiratory system, and almost perfect (>0.8) for the other organ systems. To assess accuracy, the physicians' scores were compared with a gold standard based on consensus of two experts. The total SOFA score was correct in 53% (n = 158) of the cases. The mean of the absolute deviations of the recorded total SOFA scores from the gold standard total SOFA scores was 0.82. Common causes of errors were inattention, calculation errors, and misinterpretation of scoring rules. CONCLUSIONS: The results of this study indicate that the reliability and the accuracy of SOFA scoring among physicians are good. We advise implementation of additional measures to further improve reliability and accuracy of SOFA scoring.     

Recombinant human soluble thrombomodulin improves mortality in patients with sepsis especially for severe coagulopathy: a retrospective study

Background

Disseminated intravascular coagulation (DIC) is associated with high mortality in patients with sepsis. Several studies reporting that recombinant human soluble thrombomodulin (rhTM) reduced mortality in sepsis patients. This retrospective cohort study aimed to evaluate the efficacy of rhTM for patients with mild coagulopathy compared with those with severe coagulopathy.

Methods

We evaluated about 90-day mortality and SOFA score. SOFA score was also evaluated for the following components: respiratory, cardiovascular, hepatic, renal and coagulation.

Results

All 69 patients were diagnosed with sepsis, fulfilled Japanese Association for Acute Medicine criteria for DIC, and were treated with rhTM. Patients were assigned to either the mild coagulopathy group (did not fulfill the International Society on Thrombosis and Haemostasis overt DIC criteria) or the severe coagulopathy group (fulfilled overt DIC criteria). The 90-day mortality was significant lower in severe coagulopathy group than mild coagulopathy group (P?=?0.029). Although the SOFA scores did not decrease in the mild coagulopathy group, SOFA scores decreased significantly in the severe coagulopathy group. Furthermore the respiratory component of the SOFA score significant decreased in severe coagulopathy group compared with mild coagulopathy group.

Conclusions

rhTM administration may reduce mortality by improving organ dysfunction especially for respiratory in septic patients with severe coagulopathy.

     

危重病评分系统预测急性肾损伤患者预后优于RIFLE分级

目的评价并比较序贯性脏器衰竭评分(sequential organ failure assessment,SOFA)、急性生理学与慢性健康状况评分(acute physiology and chronic health evaluation,APACHE)Ⅱ、简明急性生理学评分(simplified acute physiology score,SAPS)Ⅱ和Liano评分4种危重病评分系统及RIFLE标准对急性肾损伤(acute kidney injury,AKI)患者的预后评估价值。方法本研究为前瞻性、单中心研究,收集2008年12月到2009年11月复旦大学附属华山医院各种病因引起的AKI患者。AKI的诊断标准为RIFLE的肌酐标准,除外肾后性、肾小球性、肾血管性和间质性肾炎等引起的急性损伤。研究的主要终点是28d死亡率。比较存活组和死亡组的RIFLE分级、SOFA、APACHEⅡ、SAPSⅡ和Liano评分,并进行各种评分系统对死亡的ROC曲线分析,同时将4种评分方法根据RIFLE分级进行分层分析。结果共入选194例符合入选标准的AKI患者。存活组和死亡组的RIFLE分级、AKI病因、是否需要透析差异无统计学意义(P0.05)。死亡组的机械通气比例、SOFA、APACHEⅡ、SAPSⅡ和Liano评分显著高于存活组(P0.001)。SOFA、APACHEⅡ、SAPSⅡ和Liano评分预测死亡的受试者工作特性(ROC)曲线下面积分别为0.900、0.885、0.888、0.875(均P0.001),而RIFLE的ROC曲线下面积为0.566(P0.05)。按AKI的RIFLE级别进行分层分析时发现,4个评分方法在衰竭组(Fc)ROC曲线下面积最大,其中又以Liano评分最高。结论 RIFLE分级对AKI患者的预后无明显的判断价值,而危重病评分包括SOFA、APACHEⅡ、SAPSⅡ和Liano评分对AKI的预后具有良好的预测价值。     

New diagnostic strategy for sepsis-induced disseminated intravascular coagulation: a prospective single-center observational study

Introduction

Inflammation and coagulation are closely interrelated pathophysiologic processes in the pathogenesis of sepsis. However, the diagnostic criteria of sepsis and disseminated intravascular coagulation (DIC) are different. This study aimed to define a biomarker panel to predict sepsis-induced DIC in emergency department patients.

Methods

Eighty-two patients who were admitted to the emergency department of a tertiary university hospital were included in this study. The inclusion criteria were as follows: (1) age >18 years; (2) ≥1 systemic inflammatory response syndrome (SIRS) criteria. Patients were excluded if they lacked biomarker data or apparent clinical manifestations. Eleven biomarkers were assayed from blood drawn on ED admission. Receiver operating curve (ROC) analysis including the area under the ROC and multivariable logistic regression were used to identify an optimal combination of biomarkers to create a diagnostic panel. The derived formula for weighting biomarker values was used to determine the severity of sepsis-induced DIC, which was divided into three categories: mild, moderate, and severe. We also investigated the ability of this classification to predict secondary outcome measures of rates of sepsis and DIC, DIC score, acute physiology and chronic health evaluation (APACHE) II score, sequential organ failure score (SOFA) score, and 28-day all-cause mortality.

Results

Among the 11 biomarkers tested, the optimal 2-marker panel comprised presepsin and protein C. The area under the curve for the accuracies of predicting sepsis and DIC from these two biomarkers were 0.913 and 0.880, respectively. When patients were divided according to the severity of sepsis-induced DIC, all secondary outcomes except for mortality were significantly higher depending on the severity (P < .0001). The overall mortality rates of mild, moderate, and severe sepsis-induced DIC were 7.14%, 15.4%, and 28.6%, respectively (P = .0994).

Conclusions

A biomarker panel of presepsin and protein C is predictive of the severity of sepsis-induced DIC in suspected ED patients. These criteria for sepsis-induced DIC are very simple, easy to implement, and can be used in intensive care units as a point-of-care test.