Early coagulation disorders after severe burn injury: impact on mortality

Objective To evaluate the time course of coagulation markers in the early postburn period and clarify the role of coagulation alterations in organ failure and in mortality prognosis. Design and setting This prospective study was conducted in the burn ICU of a tertiary hospital. Patients 45 patients with severe thermal burn injury. Measurements and results Clinical data and coagulation and fibrinolysis parameters were measured during the first postburn week. The ICU 28-day mortality rate was 33%. Significant differences in the time course of coagulation markers were observed between survivors and nonsurvivors. SOFA score distinguished between patients with overt and nonovert disseminated intravascular coagulation (DIC) during the overall investigation period. Presence of overt DIC was related to mortality (OR = 0.1). Antithrombin, protein S, plasminogen activator inhibitor 1, and SOFA score on day 3, protein C on day 5, and thrombin/antithrombin complexes on day 7 revealed a good prognostic value for ICU mortality, according to the area under ROC curves. Conclusions Severe thermal injury is associated with the early activation of coagulation cascade, presence of DIC, organ failure, and increased mortality.     

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。     

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.     

Effects of antithrombin and gabexate mesilate on disseminated intravascular coagulation: a preliminary study

Purpose

We hypothesized that antithrombin is more effective for disseminated intravascular coagulation (DIC) than is gabexate mesilate, which is a protease inhibitor, suggested from the previous studies. Initially, we compared the effects of antithrombin and gabexate mesilate for treating infection-related DIC.

Methods

Sixteen adult patients with a diagnosis of DIC with infection who were assessed with an acute DIC score 4 or higher at the admission to the intensive care unit were divided into antithrombin-treated and gabexate mesilate–treated groups. White blood cell counts, C-reactive protein, platelet counts, antithrombin, fibrin and fibrinogen degradation product, d-dimer, fibrinogen, thrombin antithrombin complex, plasmin plasminogen complex, prothrombin time, and activated partial thrombin time were measured on the day of admission and on days 1, 3, 5, and 7 thereafter. Mortality over 28 days was also compared.

Results

Platelet counts and antithrombin were significantly higher in the antithrombin group on day 7 and on days 5 and 7, respectively. Antithrombin increased to the normal level on day 1 in the antithrombin group but on day 7 in the gabexate mesilate group. C-reactive protein, fibrinogen degradation product, d-dimer, thrombin antithrombin complex, plasmin plasminogen complex, and prothrombin time were lower in the antithrombin group; but the differences were not significant. The 28-day mortality was 2 of 8 in the antithrombin group and 3 of 8 in the gabexate mesilate group, but they were not significantly different.

Conclusions

Antithrombin may be a more effective treatment for coagulation and fibrinolysis disorders than gabexate mesilate in infection-related DIC, but there was no difference in 28-day mortality.     

A multicenter, prospective validation of disseminated intravascular coagulation diagnostic criteria for critically ill patients: comparing current criteria

OBJECTIVES: To validate scoring algorithm criteria established by the Japanese Association for Acute Medicine (JAAM) for disseminated intravascular coagulation (DIC) and to evaluate its diagnostic property by comparing the two leading scoring systems for DIC, from the Japanese Ministry of Health and Welfare (JMHW) and International Society on Thrombosis and Haemostasis (ISTH). DESIGN: Prospective, multicenter study during a 3-month period. SETTING: General critical care center in a tertiary care hospital. Patients: Two hundred seventy-three patients with platelet counts<150x109/L were enrolled. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The JAAM, JMHW, and ISTH DIC scoring algorithms were prospectively applied within 12 hrs of patients meeting the inclusion criteria (day 0) to days 1-3, by global coagulation tests. The numbers of systemic inflammatory response syndrome (SIRS) criteria and Sequential Organ Failure Assessment (SOFA) scores were determined simultaneously. Mortality associated with any cause was also assessed 28 days after the enrollment. All global coagulation tests and SIRS criteria adopted in the JAAM criteria and their cutoff points were validated with use of SOFA scores and mortality rate. DIC diagnostic rate of the JAAM DIC scoring system was significantly higher than that of the other two criteria (p<.001). The JAAM DIC algorithm was the most sensitive for early diagnosis of DIC (p<.001). Patients who fulfilled the JAAM DIC criteria included almost all those whose DIC was diagnosed by the JMHW and ISTH scoring systems. The JAAM DIC scores showed significant correlation with SOFA scores ([rho]=0.499; p<.001). SOFA score and mortality rate worsened in accordance with an increase in the JAAM DIC score. Fibrinogen criteria had little effect in predicting outcome for the DIC patients, and a total score of 4 points in the JAAM scoring system without fibrinogen was closely related to poor prognosis. According to the results, we revised the JAAM criteria by excluding fibrinogen and confirmed that the DIC diagnostic properties of original criteria remained unchanged in the revised JAAM criteria. CONCLUSIONS: The JAAM scoring system has an acceptable property for the diagnosis of DIC. The scoring system identified most of the patients diagnosed by the JMHW and ISTH criteria. Revised JAAM DIC criteria preserved all properties of the original criteria for DIC diagnosis. The revised scoring system can be useful for selecting DIC patients for early treatment in a critical care setting.     

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。     

Simple coagulation tests improve survival prediction in patients with septic shock

Summary.  Background:  Classic mortality prediction models in intensive care units (ICUs) are based on clinical scores, which do not contain any coagulation test (SAPS-II or SOFA scores). Objectives:  To determine whether coagulation tests can improve mortality prediction in patients with septic shock. Patients and methods:  One hundred fifty-eight consecutive patients with septic shock entering our institution's ICU were investigated on the first day of admission, and deaths were registered during the first month. Results:  Among all the coagulation tests performed, only the fibrinogen (Fg) plasma level, together with the SAPS-II score and the age, were included in our simplified mortality score [area under the receiver operating curve (AUC) 0.927, standard deviation (SD) 0.030], which was more efficient than SAPS-II and SOFA scores themselves in predicting first-week mortality, its optimized cut-off having a very high negative predictive value (NPV) [0.989; 95% confidence interval (CI) 0.967–1.000)]. A simplified score predicting first-month mortality, containing the prothrombin ratio and the antithrombin activity values in addition to the age, the hemoglobin concentration, and the SAPS-II and SOFA scores (AUC 0.889, SD 0.026), was found to be superior to the SAPS-II and SOFA scores, the optimized cut-off value having a high NPV (0.952; 95% CI 0.888–1.000). Conclusions:  In patients admitted to an ICU with septic shock, some initial coagulation test values can help identify those who will survive in the first week and then in the first month.     

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.     

Combination of thrombin-antithrombin complex,plasminogen activator inhibitor-1, and protein C activity for early identification of severe coagulopathy in initial phase of sepsis: a prospective observational study

Introduction

Current criteria for early diagnosis of coagulopathy in sepsis are limited. We postulated that coagulopathy is already complicated with sepsis in the initial phase, and severe coagulopathy or disseminated intravascular coagulation (DIC) becomes overt after progressive consumption of platelet and coagulation factors. To determine early diagnostic markers for severe coagulopathy, we evaluated plasma biomarkers for association with subsequent development of overt DIC in patients with sepsis.

Methods

A single-center, prospective observational study was conducted in an adult ICU at a university hospital. Plasma samples were obtained from patients with sepsis at ICU admission. Fourteen biomarkers including global markers (platelet count, prothrombin time, activated partial thromboplastin time, fibrinogen and fibrin degradation product (FDP)); markers of thrombin generation (thrombin-antithrombin complex (TAT) and soluble fibrin); markers of anticoagulants (protein C (PC) and antithrombin); markers of fibrinolysis (plasminogen, α₂-plasmin inhibitor (PI), plasmin-α₂-PI complex, and plasminogen activator inhibitor (PAI)-1); and a marker of endothelial activation (soluble E-selectin) were assayed. Patients who had overt DIC at baseline were excluded, and the remaining patients were followed for development of overt DIC in 5 days, and for mortality in 28 days.

Results

A total of 77 patients were enrolled, and 37 developed overt DIC within the following 5 days. Most patients demonstrated hemostatic abnormalities at baseline with 98.7% TAT, 97.4% FDP and 88.3% PC. Most hemostatic biomarkers at baseline were significantly associated with subsequent development of overt DIC. Notably, TAT, PAI-1 and PC discriminated well between patients with and without developing overt DIC (area under the receiver operating characteristic curve (AUROC), 0.77 (95% confidence interval, 0.64 to 0.86); 0.87 (0.78 to 0.92); 0.85 (0.76 to 0.91), respectively), and using the three together, significantly improved the AUROC up to 0.95 (vs. TAT, PAI-1, and PC). Among the significant diagnostic markers for overt DIC, TAT and PAI-1 were also good predictors of 28-day mortality (AUROC, 0.77 and 0.81, respectively).

Conclusions

Severe coagulation and fibrinolytic abnormalities on ICU admission were associated with subsequent development of overt DIC. A single measurement of TAT, PAI-1, and PC activity could identify patients with ongoing severe coagulopathy, early in the course of sepsis.     

Disseminated intravascular coagulation score is associated with mortality for children with shock

Objective  To evaluate the association between disseminated intravascular coagulation (DIC) score and mortality for children with shock. Design  Retrospective. Setting  Tertiary care, 20-bed pediatric intensive care unit. Patients  A total of 132 children with sepsis or shock admitted from January 2003 to December 2005. Measurements and results  A total of 132 patients less than 18 years of age with a diagnosis of shock or sepsis were included in the analysis. Of these patients, 90 survived and 42 died (31.8%). Patients ranged from 6 days to 18 years (median 5.8 years), and were a majority male (63%). Variables associated with mortality included peak DIC score within 24 h of ICU admission, age, weight, volume of blood products transfused, inotrope score, pediatric index of mortality (PIM 2) score, 12-h pediatric risk of mortality (PRISM III) score and presence of mechanical ventilation (P < 0.05). Patients with DIC scores ≥ 5 (overt DIC) had 50% mortality, compared to 20% for patients with DIC scores < 5. Overall, a one-point rise in DIC score was associated with an increased risk of mortality after adjusting for age, race, gender, hemodynamic instability, and PRISM III score [OR 1.35 (1.02, 1.78)]. Most patients achieve their peak DIC score within 2 h of ICU admission. Conclusions  This analysis suggests that DIC score, easily calculated early in ICU admission, is associated with mortality for children with sepsis and shock, regardless of initial severity of illness or inotrope use.     

多指标协同应用在危重症合并血小板减少患者诊断DIC中的作用

目的通过对危重症治疗过程中出现血小板减少的患者进行观察,并进行有关凝血功能的检查,以争取早期发现、诊断弥漫性血管内凝血（DIC）。方法纳入出现血小板减少的危重症患者56例,进行DIC全套检查,并根据国际血栓与出血性疾病协会DIC诊断评分标准诊断DIC26例,根据四格表法分别对凝血酶原时间（PT）、部分活化凝血酶原时间（APTT）、凝血酶时间（TT）、纤维蛋白原总量（Fg）、抗凝血酶Ⅲ（ATⅢ）以及出血（包括皮下出血及淤斑）的敏感性、特异性、准确性、似然比及预测值进行诊断。结果PT延长、Fg降低的诊断特异性为87．0％;ATⅢ降低以及出现PT延长、Fg降低或出血三者之一诊断DIC的敏感性为96．0％。结论以血小板减少为基础的多指标联合诊断DIC可提高敏感性和特异性。     

Is protease inhibitor a choice for the treatment of pre- or mild disseminated intravascular coagulation?

OBJECTIVE: To investigate the effect of a protease inhibitor, gabexate mesylate, on patients with pre- or mild disseminated intravascular coagulation (DIC) in comparison with a control group receiving no anticoagulation therapy. DESIGN: Prospective, randomized, controlled study. SETTING: General intensive care unit at a general hospital. PATIENTS: Adult patients (40) with a DIC score between 6 and 8 (pre- or mild DIC). INTERVENTIONS: In 20 patients, gabexate mesylate (2 mg/kg/hr) was administered as 2 mL/hr in saline (treated group) and in another 20 patients, saline (2 mL/hr; control group) was administered during the study (7 days). MEASUREMENTS AND MAIN RESULTS: The following variables were determined at the time of admission to the intensive care unit before treatment and 1, 3, 5, and 7 days thereafter: platelet count, antithrombin III activity, serum or plasma concentrations of fibrinogen, fibrin degradation product, D-dimer, fibrin monomer, thrombin-antithrombin III complex, and plasmin-plasmin inhibitor complex, prothrombin time ratio, and DIC score. Two patients in the treated group and four in the control group were excluded from the study because they died during the study; therefore, 34 patients were analyzed. The measured variables of coagulation and fibrinolysis were not significantly different between the two groups, except for the D-dimer on day 3 (the treated group showed a higher concentration). D-dimer concentration and DIC score went down more quickly in the control group than the treated group, but not significantly. The mortality rate at 1 month was 40% (8 of 20) in the treated group and 35% (7 of 20) in the control group, without any differences between the two groups. CONCLUSIONS: In a limited number of patients (n = 34), gabexate mesylate (2 mg/kg/hr) could not inhibit coagulation or fibrinolysis and gabexate mesylate could not improve the DIC score or mortality rate in pre- or mild DIC.     

Cell-free plasma DNA as a predictor of outcome in severe sepsis and septic shock

BACKGROUND: Increased concentrations of cell-free DNA have been found in plasma of septic and critically ill patients. We investigated the value of plasma DNA for the prediction of intensive care unit (ICU) and hospital mortality and its association with the degree of organ dysfunction and disease severity in patients with severe sepsis. METHODS: We studied 255 patients with severe sepsis or septic shock. We obtained blood samples on the day of study inclusion and 72 h later and measured cell-free plasma DNA by real-time quantitative PCR assay for the beta-globin gene. RESULTS: Cell-free plasma DNA concentrations were higher at admission in ICU nonsurvivors than in survivors (median 15 904 vs 7522 genome equivalents [GE]/mL, P < 0.001) and 72 h later (median 15 176 GE/mL vs 6758 GE/mL, P = 0.004). Plasma DNA values were also higher in hospital nonsurvivors than in survivors (P = 0.008 to 0.009). By ROC analysis, plasma DNA concentrations had moderate discriminative power for ICU mortality (AUC 0.70-0.71). In multiple regression analysis, first-day plasma DNA was an independent predictor for ICU mortality (P = 0.005) but not for hospital mortality. Maximum lactate value and Sequential Organ Failure Assessment score correlated independently with the first-day plasma DNA in linear regression analysis. CONCLUSIONS: Cell-free plasma DNA concentrations were significantly higher in ICU and hospital nonsurvivors than in survivors and showed a moderate discriminative power regarding ICU mortality. Plasma DNA concentration was an independent predictor for ICU mortality, but not for hospital mortality, a finding that decreases its clinical value in severe sepsis and septic shock.     

Massive pulmonary embolism leading to cardiac arrest is associated with consumptive coagulopathy presenting as disseminated intravascular coagulation

See also Levi M. Disseminated intravascular coagulation or extended intravascular coagulation in massive pulmonary embolism. This issue, pp 1475–6; Thachil J. DIC score predicts mortality in massive clot coagulopathy as a result of extensive pulmonary embolism: a rebuttal. This issue, pp 1657–8; Leitner JM, Janata‐Schwatzek K, Spiel AO, Sterz F, Laggner AN, Jilma B. DIC score predicts mortality in massive clot coagulopathy as a result of extensive pulmonary embolism: reply to a rebuttal. This issue, pp 1658–9. Summary. Background: A consumptive coagulopathy resembling disseminated intravascular coagulation (DIC) has been seen in patients with massive pulmonary embolism (PE). We hypothesized that a DIC‐like condition is relevant in patients whose pulmonary embolism leads to cardiopulmonary arrest and cardiopulmonary resuscitation (CPR). Methods: This hypothesis was tested by the use of a database consisting of all cases of PE diagnosed at the Department of Emergency Medicine from June 1993 to October 2007. Out of 1018 cases with PE, 113 patients underwent CPR. In this cohort study, the resuscitated patients were compared with those with PE but without CPR. Results: Patients with PE and CPR had 3‐fold higher D‐dimer, prolonged prothrombin time (PT), reduced platelet counts and lower fibrinogen and antithrombin (AT) levels compared with PE patients without cardiac arrest (P < 0.001 for all). Among patients with PE and CPR, D‐dimer was abnormal in 100%, PT in 44%, AT in 53%, fibrinogen in 19% and platelets in 25%. In comparison, PE without CPR was associated with abnormal D‐dimer in 99%, abnormal PT in 15%, low AT in 6%, low fibrinogen in 1% and low platelets in 2%. Nine per cent of the resuscitated patients had a DIC score ≥ 5, indicating overt DIC. The DIC score highly correlated with 1‐year and in‐hospital mortality. Conclusions: Massive PE leading to CPR is associated with consumptive coagulopathy and overt DIC. In resuscitated patients, DIC markers may indicate pulmonary embolism as the underlying cause of arrest.     

弥散性血管内凝血评分在脓毒症中的应用

目的 研究弥散性血管内凝血(DIC)评分系统与脓毒症患者病情评估及预后间的关系.方法 回顾性分析2005年1月-2008年12月本院重症监护病房(ICU)收治315例脓毒症患者的资料,按住院28 d的预后分为生存组(194例)与死亡组(121例).比较两组患者血小板计数(PLT)、纤维蛋白原(Fib)、凝血酶原时间(PT)及纤维蛋白单体的差异;用logistic单因素回归分析急性生理学与慢性健康状况评分系统Ⅱ(APACHEⅡ)评分、DIC评分与预后的关系,评价APACHEⅡ评分、DIC评分在脓毒症诊断中的价值.结果 死亡组PLT、Fib显著低于生存组,PT、活化部分凝血活酶时间(APTT)、凝血时间(ACT)和纤维蛋白单体值显著高于生存组,且APACHEⅡ评分、DIC评分显著高于生存组(P<0.05或P<0.01).APACHEⅡ评分、DIC评分与脓毒症预后间均呈显著正相关[DIC评分:χ2=17.741,P<0.001,优势比(OR)=1.413,95%可信区间(CI)为1.203～1.659;APACHEⅡ评分:χ2=36.456,P<0.001,OR=1.109,95%CI为1.072～1.147].APACHEⅡ评分曲线下面积(0.706)高于DIC评分曲线下面积(0.611).结论 APACHEⅡ评分、DIC评分均可作为脓毒症预后的预测指标,但DIC评分对脓毒症的诊断和预后判断价值低于APACHEⅡ评分.     

Epidemiology of severe sepsis in Japanese intensive care units: A prospective multicenter study

Severe sepsis is a leading cause of morbidity and mortality in the intensive care unit (ICU). We conducted a prospective multicenter study to evaluate epidemiology and outcome of severe sepsis in Japanese ICUs. The patients were registered at 15 general critical care centers in Japanese tertiary care hospitals when diagnosed as having severe sepsis. Of 14,417 patients, 624 (4.3%) were diagnosed with severe sepsis. Demographic and clinical characteristics at enrollment (Day 1), physiologic and blood variables on Days 1 and 4, and mortality were evaluated. Mean age was 69.0 years, and initial mean Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores were 23.4 and 8.6, respectively. The 28-day mortality was 23.1%, and overall hospital mortality was 29.5%. SOFA score and disseminated intravascular coagulation (DIC) score were consistently higher in nonsurvivors than survivors on Days 1 and 4. SOFA score, DIC score on Days 1 and 4, and hospital mortality were higher in patients with than without septic shock. SOFA score on Days 1 and 4 and hospital mortality were higher in patients with than without DIC. Logistic regression analyses showed age, presence of septic shock, DIC, and cardiovascular dysfunction at enrollment to be predictors of 28-day mortality and presence of comorbidity to be an additional predictor of hospital mortality. Presence of septic shock or DIC resulted in approximately twice the mortality of patients without each factor, whereas the presence of comorbidity may be a significant predictor of delayed mortality in severe sepsis.     

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.     

Predictive value of antithrombin III and serum C-reactive protein concentration in critically ill patients with suspected sepsis

OBJECTIVE: To evaluate at admission the performance of serum antithrombin III, serum C-reactive protein, white blood cell and platelet counts, and thromboplastin time values in prediction of hospital mortality rates in critically ill patients with suspected sepsis. DESIGN: Prospective, cohort study. SETTING: University hospital medical-surgical intensive care unit. PATIENTS: One hundred eight consecutive critically ill patients with suspected sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The outcome measure was hospital mortality rate. Hospital survivors (n = 66) and nonsurvivors (n = 42) differed statistically significantly in admission antithrombin III activity (percentage of normal): survivors' median 66% (interquartile range, 48% to 82%) vs. nonsurvivors' median 46% (37% to 65%, p =.0002 by Mann-Whitney test). Analysis revealed similarly statistically significant differences between survivors and nonsurvivors in admission platelet count, admission thromboplastin time, day 1 Logistic Organ Dysfunction score, and Acute Physiology and Chronic Health Evaluation III score, but not in serum C-reactive protein concentrations or in white blood cells. However, the areas under the receiver operating curves (AUC) showed significantly worse discriminative power for admission antithrombin III concentration (AUC, 0.71; SE, 0.05), platelet count (AUC, 0.67; SE, 0.05), thromboplastin time (AUC, 0.65; SE, 0.05), C-reactive protein concentration (AUC, 0.60; SE, 0.05), and white blood cell count (AUC, 0.53; SE, 0.06) than did the day 1 Logistic Organ Dysfunction score (AUC, 0.82; SE, 0.04) and the Acute Physiology and Chronic Health Evaluation III score (AUC, 0.84; SE, 0.04). Multivariate logistic regression analysis revealed that only the Acute Physiology and Chronic Health Evaluation III score was independently associated with hospital mortality rate. CONCLUSIONS: Admission antithrombin III concentrations, but not C-reactive protein concentrations, differ significantly between hospital survivors and nonsurvivors among critically ill patients with septic infection. However, in prediction of hospital mortality rate, the discriminative power of admission antithrombin III concentration is poor, as judged by analysis of areas under the receiver operating curves, and is not independently associated with hospital mortality rate.     

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.     

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.