disseminated intravascular coagulation

弥散性血管内凝血
  • 文章类型: Journal Article
    弥散性血管内凝血(DIC)具有很高的死亡风险,然而,它的确切影响仍然存在争议。本研究调查了脓毒症患者DIC与死亡率的关系。强调多器官功能。利用北京大学人民医院脓毒症相关性凝血病数据库的调查数据,我们根据入住ICU24小时内的DIC评分(<5个临界值)将患者分为DIC和非DIC组.ICU死亡率是主要结果。在倾向评分匹配(PSM)后对死亡率因素进行逻辑回归分析之前进行了初始数据比较。采用中介分析估计的直接和间接关联。在549名参与者中,131人属于DIC组,其余418在非DIC组中。基线特征呈现后,进行了PSM,显示出非血小板序贯器官衰竭评估(nonplt-SOFA)评分(6.3±2.7vs5.0±2.5,P<0.001)和住院死亡率(47.3%vs29.5%,DIC组P=0.003)。DIC与住院死亡率之间存在显著相关性(OR2.15,95%CI1.29-3.59,P=0.003),以nonplt-SOFA评分(OR1.16,95%CI1.05-1.28,P=0.004)和出血(OR2.33,95%CI1.08-5.03,P=0.032)作为预测因子。总体效应大小为0.1786(95%CI0.0542-0.2886),包括直接效应大小为0.1423(95%CI0.0153-0.2551)和间接效应大小为0.0363(95%CI0.0034-0.0739),约有20.3%的效应介导。这些发现强调了DIC与脓毒症患者死亡风险增加的相关性。敦促将抗凝重点放在出血管理上,与器官功能障碍评估推荐抗凝治疗疗效。
    Disseminated intravascular coagulation (DIC) poses a high mortality risk, yet its exact impact remains contentious. This study investigates DIC\'s association with mortality in individuals with sepsis, emphasizing multiple organ function. Using data from the Peking University People\'s Hospital Investigation on Sepsis-Induced Coagulopathy database, we categorized patients into DIC and non-DIC groups based on DIC scores within 24 h of ICU admission (< 5 cutoff). ICU mortality was the main outcome. Initial data comparison preceded logistic regression analysis of mortality factors post-propensity score matching (PSM). Employing mediation analysis estimated direct and indirect associations. Of 549 participants, 131 were in the DIC group, with the remaining 418 in the non-DIC group. Following baseline characteristic presentation, PSM was conducted, revealing significantly higher nonplatelet sequential organ failure assessment (nonplt-SOFA) scores (6.3 ± 2.7 vs 5.0 ± 2.5, P < 0.001) and in-hospital mortality rates (47.3% vs 29.5%, P = 0.003) in the DIC group. A significant correlation between DIC and in-hospital mortality persisted (OR 2.15, 95% CI 1.29-3.59, P = 0.003), with nonplt-SOFA scores (OR 1.16, 95% CI 1.05-1.28, P = 0.004) and hemorrhage (OR 2.33, 95% CI 1.08-5.03, P = 0.032) as predictors. The overall effect size was 0.1786 (95% CI 0.0542-0.2886), comprising a direct effect size of 0.1423 (95% CI 0.0153-0.2551) and an indirect effect size of 0.0363 (95% CI 0.0034-0.0739), with approximately 20.3% of effects mediated. These findings underscore DIC\'s association with increased mortality risk in patients with sepsis, urging anticoagulation focus over bleeding management, with organ dysfunction assessment recommended for anticoagulant treatment efficacy.
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  • 文章类型: Journal Article
    背景:尚未建立针对产后出血(PPH)的标准治疗指南。我们旨在评估接受手术和非手术治疗的PPH患者在预后和预后方面的差异。
    方法:这项回顾性研究包括2013年8月至2023年10月在两家转诊医院诊断为PPH的230例患者。将患者分为非手术组(第1组,n=159)和手术干预组(第2组,n=71)。通过将手术干预组分为立即(n=45)和延迟手术干预组(n=26)进行亚组分析。
    结果:第2组的初始乳酸水平和休克指数显着升高(2.85±1.37vs.4.54±3.63mmol/L,p=0.001,和0.83±0.26vs.1.10±0.51,p<0.001)。相反,第2组的初始心率和体温显着降低(92.5±21.0vs.109.0±28.1拍/分,p<0.001,和37.3±0.8°Cvs.37.0±0.9°C,分别为p=0.011)。Logistic回归分析确定初始体温低,高乳酸水平,和休克指数是手术干预的独立预测因子(分别为p=0.029,p=0.027和p=0.049)。关于PPH的原因,音调在第1组中明显更普遍(57.2%vs.35.2%,p=0.002),而创伤在第2组中明显更普遍(24.5%vs.39.4%,p=0.030)。第2组的总体结果和预后比第1组差。亚组分析显示,合并其他原因的子宫收缩乏力的发生率明显更高,子宫切除术,延迟手术干预组的弥散性血管内凝血病高于立即手术干预组(42.2%vs.69.2%,p=0.027;51.1%vs.73.1%,p=0.049;和17.8%与46.2%,分别为p=0.018)。
    结论:表现为乳酸水平和休克指数升高以及体温降低的PPH患者可能是手术治疗对象。此外,对合并其他原因的PPH的宫缩乏力患者立即进行手术干预,可改善预后,减少术后并发症。
    BACKGROUND: No standard treatment guidelines have been established for postpartum hemorrhage (PPH). We aimed to assess the differences in outcomes and prognoses between patients with PPH who underwent surgical and non-surgical treatment.
    METHODS: This retrospective study included 230 patients diagnosed with PPH at two referral hospitals between August 2013 and October 2023. The patients were divided into non-surgical (group 1, n = 159) and surgical intervention groups (group 2, n = 71). A subgroup analysis was performed by dividing the surgical intervention group into immediate (n = 45) and delayed surgical intervention groups (n = 26).
    RESULTS: Initial lactic acid levels and shock index were significantly higher in group 2 (2.85 ± 1.37 vs. 4.54 ± 3.63 mmol/L, p = 0.001, and 0.83 ± 0.26 vs. 1.10 ± 0.51, p < 0.001, respectively). Conversely, initial heart rate and body temperature were significantly lower in group 2 (92.5 ± 21.0 vs. 109.0 ± 28.1 beat/min, p < 0.001, and 37.3 ± 0.8 °C vs. 37.0 ± 0.9 °C, p = 0.011, respectively). Logistic regression analysis identified low initial body temperature, high lactic acid level, and shock index as independent predictors of surgical intervention (p = 0.029, p = 0.027, and p = 0.049, respectively). Regarding the causes of PPH, tone was significantly more prevalent in group 1 (57.2% vs. 35.2%, p = 0.002), whereas trauma was significantly more prevalent in group 2 (24.5% vs. 39.4%, p = 0.030). Group 2 had worse overall outcomes and prognoses than group 1. The subgroup analysis showed significantly higher rates of uterine atony combined with other causes, hysterectomy, and disseminated intravascular coagulopathy in the delayed surgical intervention group than the immediate surgical intervention group (42.2% vs. 69.2%, p = 0.027; 51.1% vs. 73.1%, p = 0.049; and 17.8% vs. 46.2%, p = 0.018, respectively).
    CONCLUSIONS: Patients with PPH presenting with increased lactic acid levels and shock index and decreased body temperature may be surgical candidates. Additionally, immediate surgical intervention in patients with uterine atony combined with other causes of PPH could improve prognosis and reduce postoperative complications.
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  • 文章类型: Journal Article
    自2022年7月以来,日本的产科弥漫性血管内凝血(DIC)已根据新标准(暂定版本)进行诊断。评估主要的潜在疾病,纤维蛋白原水平,和纤维蛋白/纤维蛋白原降解产物或D-二聚体水平。2024年6月,暂定版本进行了小修订,最终版本发布。以前的日本标准评估潜在疾病,临床症状,和各种实验室发现。本研究旨在证明其有效性,可靠性,和新标准的有效性(最终版本)。我们分析了212例单胎妊娠妇女,这些妇女在22个妊娠周后分娩,阴道分娩时失血≥1000mL或剖宫产时失血≥2000mL。分娩时接受输血前实验室检查结果缺失的患者被排除在外。在产科DIC组中,纤维蛋白原水平<150mg/dL的频率显着高于对照组(90%vs.5%,p<0.0001),根据以前的日本标准,得分≥8的频率也是如此(100%与10%,p<0.0001)。Cronbachα为0.757,Spearman\的等级顺序相关性在新标准和以前的标准之间为0.558。总之,我们证明了有效性,可靠性,以及日本新标准(最终版本)诊断产科DIC的有效性。
    Since July 2022, obstetrical disseminated intravascular coagulation (DIC) in Japan has been diagnosed based on the new criteria (tentative version), which assesses the main underlying disease, fibrinogen level, and fibrin/fibrinogen degradation products or D-dimer level. In June 2024, the tentative version underwent minor revision and the final version was released. The previous Japanese criteria assessed underlying disease, clinical symptoms, and various laboratory findings. This study aimed to prove the effectiveness, reliability, and validity of the new criteria (final version). We analyzed 212 women with singleton pregnancies who delivered after 22 gestational weeks and experienced blood loss ≥ 1000 mL during vaginal delivery or ≥ 2000 mL during cesarean section. Those with missing laboratory findings before receiving blood transfusion at delivery were excluded. In the obstetrical DIC group, the frequency of fibrinogen levels < 150 mg/dL was significantly higher than in the control group (90% vs. 5%, p < 0.0001), as was the frequency of scores ≥ 8 according to the previous Japanese criteria (100% vs. 10%, p < 0.0001). Cronbach alpha was 0.757 and Spearman\'s rank-order correlation was 0.558 between the new and previous criteria. In conclusion, we proved the effectiveness, reliability, and validity of the Japanese new criteria (final version) to diagnose obstetrical DIC.
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  • 文章类型: Journal Article
    弥散性血管内凝血(DIC)是一种破坏性疾病,这总是导致重症监护病房危重患者的不良预后。关于DIC患者短期死亡率预测的研究很少。本研究旨在确定导致DIC死亡率的危险因素并构建预测列线图。
    共纳入676例显性DIC患者。基于使用最小绝对收缩和选择算子(LASSO)回归确定的协变量,开发了Cox比例风险回归模型。在MIMIC-III和MIMIC-IV临床数据库中独立评估了预测性能,以及第908医院数据库(908thH)。使用MIMIC-III独立评估模型性能,MIMIC-IV,和第908医院临床数据库。
    Cox模型结合了Lasso回归确定的变量,包括心力衰竭,脓毒症,高度,SBP,乳酸水平,HCT,PLT,INR,AST,和去甲肾上腺素的使用。该模型有效地将患者分为不同的死亡风险组,MIMIC-III的C指数>0.65,MIMIC-IV,第908医院数据库。模型在7天和28天的校准曲线表明预测性能良好。然后,开发了列线图以促进结果可视化。决策曲线分析表明,列线图具有出色的净收益。
    这项研究提供了基于Lasso-Cox回归模型的短期公开DIC死亡风险的预测列线图,提供个性化和可靠的死亡风险预测。
    UNASSIGNED: Disseminated intravascular coagulation (DIC) is a devastating condition, which always cause poor outcome of critically ill patients in intensive care unit. Studies concerning short-term mortality prediction in DIC patients is scarce. This study aimed to identify risk factors contributing to DIC mortality and construct a predictive nomogram.
    UNASSIGNED: A total of 676 overt DIC patients were included. A Cox proportional hazards regression model was developed based on covariates identified using least absolute shrinkage and selection operator (LASSO) regression. The prediction performance was independently evaluated in the MIMIC-III and MIMIC-IV Clinical Database, as well as the 908th Hospital Database (908thH). Model performance was independently assessed using MIMIC-III, MIMIC-IV, and the 908th Hospital Clinical Database.
    UNASSIGNED: The Cox model incorporated variables identified by Lasso regression including heart failure, sepsis, height, SBP, lactate levels, HCT, PLT, INR, AST, and norepinephrine use. The model effectively stratified patients into different mortality risk groups, with a C-index of >0.65 across the MIMIC-III, MIMIC-IV, and 908th Hospital databases. The calibration curves of the model at 7 and 28 days demonstrated that the prediction performance was good. And then, a nomogram was developed to facilitate result visualization. Decision curve analysis indicated superior net benefits of the nomogram.
    UNASSIGNED: This study provides a predictive nomogram for short-term overt DIC mortality risk based on a Lasso-Cox regression model, offering individualized and reliable mortality risk predictions.
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  • 文章类型: News
    背景:将DIC与肝病的凝血病区分开来是一个共同的临床挑战。这里,我们评估了两种常用诊断工具的临床应用价值:因子VIII(FVIII)水平和ISTHDIC评分.
    方法:为此,我们对DIC患者进行了回顾性图表回顾,肝病,或者两者兼而有之。进行多元逻辑回归并生成受试者操作特征曲线以计算曲线下面积(AUC),用于区分肝病背景下的DIC。
    结果:在123例DIC患者中,肝病,或者肝病加DIC,FVIII水平没有显著差异。DIC患者的ISTH评分低于有或没有DIC的肝病患者。增加了几个实验室参数,包括MPV,FV,FVIII,INR,和PTT,ISTHDIC评分提高了区分DIC在肝病中与单独肝病的AUC(AUC=0.76;P<0.0001)。
    结论:我们得出结论,FVIII水平不能区分DIC和肝脏疾病,ISTHDIC评分不能预测肝病患者的DIC。在ISTHDIC评分中包含其他实验室变量可能有助于识别肝病患者的DIC。
    BACKGROUND: Distinguishing disseminated intravascular coagulation (DIC) from the coagulopathy of liver disease represents a common clinical challenge. Here, we evaluated the utility of two diagnostic tools frequently used to differentiate between these conditions: factor VIII (FVIII) levels and the International Society on Thrombosis and Hemostasis (ISTH) DIC score.
    METHODS: To this end, we conducted a retrospective chart review of patients with DIC, liver disease, or both. Multiple logistic regression was performed, and receiver operating characteristic curves were generated to calculate the area under curve (AUC) for distinguishing DIC in the setting of liver disease.
    RESULTS: Among 123 patients with DIC, liver disease, or liver disease plus DIC, FVIII levels did not differ significantly. ISTH scores were lower in patients with DIC than in liver disease with or without DIC. Addition of several laboratory parameters to the ISTH score, including mean platelet volume, FV, FVIII, international normalized ratio, and activated partial thromboplastin time, improved AUC for distinguishing DIC in liver disease from liver disease alone (AUC = 0.76; p < 0.0001).
    CONCLUSIONS: We conclude that FVIII levels do not distinguish DIC from liver disease, and ISTH DIC scores are not predictive of DIC in patients with liver disease. Inclusion of additional lab variables within the ISTH DIC score may aid in identifying DIC in patients with liver disease.
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  • 文章类型: Journal Article
    最近,与热有关的疾病的发病率呈稳步上升趋势,与气候变化和空气污染等环境因素密切相关。与热有关的疾病的进展是一个连续的过程,可以进展到终末期,当它转变为中暑时,最严重的形式。中暑的主要原因是核心体温高于40°C和中枢神经系统功能障碍。目前的知识表明,中暑的发病机制是复杂多样的,包括炎症反应,氧化应激,细胞死亡,和凝血功能障碍。本文综述了中暑的病理生理学和发病机制的研究进展。专注于相关的分子机制。此外,我们回顾了中暑的常见策略,并整理了中暑各个临床前阶段的药物,旨在为未来更深入地研究中暑的机制和降低中暑死亡率提供全面的研究路线图。
    Recently, the incidence of heat-related illnesses has exhibited a steadily upward trend, which is closely associated with several environmental factors such as climate change and air pollution. The progression of heat-related illnesses is a continuous process and can progress to the terminal period when it transforms into heat stroke, the most severe form. Heat stroke is markedly by a core body temperature above 40°C and central nervous system dysfunction. Current knowledge suggests that the pathogenesis of heat stroke is complex and varied, including inflammatory response, oxidative stress, cell death, and coagulation dysfunction. This review consolidated recent research progress on the pathophysiology and pathogenesis of heat stroke, with a focus on the related molecular mechanisms. In addition, we reviewed common strategies and sorted out the drugs in various preclinical stages for heat stroke, aiming to offer a comprehensive research roadmap for more in-depth researches into the mechanisms of heat stroke and the reduction in the mortality of heat stroke in the future.
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  • 文章类型: Case Reports
    背景:D-二聚体,交联纤维蛋白降解的特定产物,在血栓性疾病的早期诊断和监测溶栓疗效方面具有重要的临床价值;因此,D-二聚体检测结果的准确性至关重要。
    方法:本文报道一例弥漫性血管内凝血(DIC)患者,由于钩效应导致D-二聚体出现假降低。
    结果:DIC患者的三项D-二聚体检测结果为1.09mg/L,0.93mg/L,和1.43毫克/升样品稀释后,结果为:首次(1:128)842.24mg/L,第二次(1:128)1,505.28mg/L,第三次(1:32)415.68mg/L稀释前后三次检测结果有显著性差异,因为D-二聚体浓度太高,超出检测范围并引起钩效应,错误地降低了D-二聚体值。
    结论:当DIC患者的D-二聚体值与临床情况不符时,应该考虑钩效应的可能性,并且可以通过样品稀释法排除错误的减少。这样,可以获得准确的临床结果,避免延误DIC患者的诊断和治疗。
    BACKGROUND: D-dimer, a specific product of cross-linked fibrin degradation, is of great clinical value in the early diagnosis of thrombotic diseases and in monitoring the efficacy of thrombolysis; therefore, the accuracy of D-dimer test results is crucial.
    METHODS: This article reports a case of a patient with disseminated intravascular coagulation (DIC) who experienced a false decrease in D-dimer due to the hook effect.
    RESULTS: The three D-dimer test results for DIC patients were 1.09 mg/L, 0.93 mg/L, and 1.43 mg/L. After sample dilution, the results were: first time (1:128) 842.24 mg/L, second time (1:128) 1,505.28 mg/L, third time (1:32) 415.68 mg/L. There was a significant difference in the three test results before and after dilution, because the D-dimer concentration was too high, exceeding the detection range and causing the hook effect, which falsely lowered the D-dimer value.
    CONCLUSIONS: When the D-dimer value of DIC patients does not match the clinical situation, the possibility of the hook effect should be considered, and the false decrease can be ruled out by the sample dilution method. In this way, accurate clinical results can be obtained to avoid delaying the diagnosis and treatment of DIC patients.
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  • 文章类型: Journal Article
    一名43岁的全血细胞减少症患者被诊断为急性早幼粒细胞白血病(APL)。在单用全反式维甲酸(ATRA)诱导治疗的第一天,他表现为高烧,并通过SARS-CoV2抗原测试发现患有2019年冠状病毒病(COVID-19)感染。虽然通常建议推迟COVID-19的APL患者的治疗,除非需要紧急APL治疗,由于APL诱导的弥散性血管内凝血(DIC),该患者需要继续治疗.考虑到区分分化综合征(DS)和COVID-19加重的挑战,ATRA剂量减少至50%。患者能够继续治疗,没有发生DS或DIC恶化,导致他从COVID-19中康复并缓解APL。
    A 43-year-old man with pancytopenia was diagnosed with acute promyelocytic leukemia (APL). On the first day of induction therapy with all-trans retinoic acid (ATRA) alone, he presented with high fever and was found to have coronavirus disease 2019 (COVID-19) infection by SARS-CoV2 antigen test. While it is generally recommended to delay treatment for APL patients with COVID-19 unless urgent APL treatment is required, this patient needed to continue treatment due to APL-induced disseminated intravascular coagulation (DIC). Considering the challenge of distinguishing between differentiation syndrome (DS) and COVID-19 exacerbation, the ATRA dosage was reduced to 50%. The patient was able to continue treatment without development of DS or exacerbation of DIC, leading to his recovery from COVID-19 and remission of APL.
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  • 文章类型: Journal Article
    背景:没有可靠的指标可以在短期内评估抗凝治疗对脓毒症相关的弥散性血管内凝血(DIC)的治疗效果。这项研究的目的是开发和验证预后指数,以确定在3天治疗后接受抗凝血酶浓缩物治疗的脓毒症DIC患者的28天死亡率。
    方法:推导队列是利用上市后调查的数据集建立的,而用于验证的队列是从日本全国脓毒症登记数据中获得的。通过单变量和多变量分析,在推导队列中确定了与28日死亡率独立相关的变量.然后根据风险预测函数为风险变量分配加权分数,导致综合指数的发展。随后,受试者工作特征曲线下面积(AUROC)。通过Kaplan-Meier分析比较28天存活。
    结果:在派生队列中,1492例患者中有252例(16.9%)在28天内死亡。多变量分析确定DIC分辨率(风险比[HR]:0.31,95%置信区间[CI]:0.22-0.45,P<0.0001)和序贯器官衰竭评估(SOFA)评分变化率(HR:0.42,95%CI:0.36-0.50,P<0.0001)被确定为死亡的独立预测因子。综合预后指数(CPI)构建为DIC分辨率(是:1,否:0)+SOFA评分变化率(第0天SOFA评分-第3天SOFA评分/第0天SOFA评分)。当CPI高于0.19时,判定患者存活。关于派生队列,存活的AUROC为0.76。至于验证队列,AUROC为0.71。
    结论:CPI可以预测接受抗凝血酶治疗的DIC脓毒症患者的28天生存率。它计算简单,易于计算,在实践中很有用。
    BACKGROUND: There is no reliable indicator that can assess the treatment effect of anticoagulant therapy for sepsis-associated disseminated intravascular coagulation (DIC) in the short term. The aim of this study is to develop and validate a prognostic index identifying 28-day mortality in septic DIC patients treated with antithrombin concentrate after a 3-day treatment.
    METHODS: The cohort for derivation was established utilizing the dataset from post-marketing surveys, while the cohort for validation was acquired from Japan\'s nationwide sepsis registry data. Through univariate and multivariate analyses, variables that were independently associated with 28-day mortality were identified within the derivation cohort. Risk variables were then assigned a weighted score based on the risk prediction function, leading to the development of a composite index. Subsequently, the area under the receiver operating characteristic curve (AUROC). 28-day survival was compared by Kaplan-Meier analysis.
    RESULTS: In the derivation cohort, 252 (16.9%) of the 1492 patients deceased within 28 days. Multivariable analysis identified DIC resolution (hazard ratio [HR]: 0.31, 95% confidence interval [CI]: 0.22-0.45, P < 0.0001) and rate of Sequential Organ Failure Assessment (SOFA) score change (HR: 0.42, 95% CI: 0.36-0.50, P < 0.0001) were identified as independent predictors of death. The composite prognostic index (CPI) was constructed as DIC resolution (yes: 1, no: 0) + rate of SOFA score change (Day 0 SOFA score-Day 3 SOFA score/Day 0 SOFA score). When the CPI is higher than 0.19, the patients are judged to survive. Concerning the derivation cohort, AUROC for survival was 0.76. As for the validation cohort, AUROC was 0.71.
    CONCLUSIONS: CPI can predict the 28-day survival of septic patients with DIC who have undergone antithrombin treatment. It is simple and easy to calculate and will be useful in practice.
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  • 文章类型: Journal Article
    凝血病,微血管改变和伴随的器官功能障碍是败血症的标志。尝试用组织因子(TF)抑制剂减弱凝血激活,即组织因子途径抑制剂(TFPI),在一组异质性的脓毒症患者中没有发现生存益处,但在国际标准化比率(INR)<1.2的患者中,潜在的生存获益。由于TF/TFPI比值的增加决定了体外微血管内皮细胞的促凝血活性,我们调查了血液中TF/TFPI比值是否与INR改变有关,器官功能障碍,弥漫性血管内凝血(DIC)与感染性休克的结局。分析了29名健康对照(HC)和89名进入三级ICU的感染性休克患者。分析血液中的TF和TFPI,并与器官功能障碍有关,DIC和死亡率。感染性休克患者的TF水平比HC高1.6倍,TFPI水平高2.9倍。与HC相比,感染性休克的TF/TFPI比率较低(0.003(0.002-0.005)与0.006(0.005-0.008),p<0.001)。与幸存者相比,非幸存者的TFPI水平更高(43038(29354-54023)与28041(21675-46582)pg/ml,p=0.011)。高TFPI水平与急性肾损伤有关,肝功能障碍,DIC和疾病严重程度。TF/TFPI比值与肌钙蛋白T呈正相关(b=0.531(0.309-0.754),p<0.001)。高TF/TFPI比率仅与心肌损伤有关,而与其他器官功能障碍无关。系统性TFPI水平似乎反映了疾病的严重程度。这些发现指出了TF/TFPI在脓毒症诱导的心肌损伤中的病理生理作用。
    Coagulopathy, microvascular alterations and concomitant organ dysfunctions are hallmarks of sepsis. Attempts to attenuate coagulation activation with an inhibitor of tissue factor (TF), i.e. tissue factor pathway inhibitor (TFPI), revealed no survival benefit in a heterogenous group of sepsis patients, but a potential survival benefit in patients with an international normalized ratio (INR) < 1.2. Since an increased TF/TFPI ratio determines the procoagulant activity specifically on microvascular endothelial cells in vitro, we investigated whether TF/TFPI ratio in blood is associated with INR alterations, organ dysfunctions, disseminated intravascular coagulation (DIC) and outcome in septic shock. Twenty-nine healthy controls (HC) and 89 patients with septic shock admitted to a tertiary ICU were analyzed. TF and TFPI in blood was analyzed and related to organ dysfunctions, DIC and mortality. Patients with septic shock had 1.6-fold higher levels of TF and 2.9-fold higher levels of TFPI than HC. TF/TFPI ratio was lower in septic shock compared to HC (0.003 (0.002-0.005) vs. 0.006 (0.005-0.008), p < 0.001). Non-survivors had higher TFPI levels compared to survivors (43038 (29354-54023) vs. 28041 (21675-46582) pg/ml, p = 0.011). High TFPI levels were associated with acute kidney injury, liver dysfunction, DIC and disease severity. There was a positive association between TF/TFPI ratio and troponin T (b = 0.531 (0.309-0.754), p < 0.001). A high TF/TFPI ratio is exclusively associated with myocardial injury but not with other organ dysfunctions. Systemic TFPI levels seem to reflect disease severity. These findings point towards a pathophysiologic role of TF/TFPI in sepsis-induced myocardial injury.
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