Sepsis-induced Coagulopathy Research Articles

Clinical characteristics and prognosis analysis of pseudomonas aeruginosa bloodstream infection in adults: a retrospective study.

Pseudomonas aeruginosa bloodstream infections (PA BSIs) in adults, especially those complicated by sepsis, are associated with high rates of morbidity and mortality. Early identification of risk factors for both mortality and sepsis-induced coagulopathy (SIC) is critical to optimizing patient management and improving outcomes. We conducted a retrospective analysis of 118 adult patients diagnosed with PA BSIs at the Affiliated Hospital of Xuzhou Medical University from January 2022 to February 2024. Univariate analysis was employed to identify significant clinical factors, followed by multivariate stepwise logistic regression to determine independent predictors of mortality and SIC. Based on these findings, nomogram models were constructed and evaluated using the area under the receiver operating characteristic curve (AUC), Bootstrap resampling, and calibration plots to assess model performance. Empiric sensitive antibiotic therapy (ESAT) (OR = 0.039, P < 0.001), coronary artery disease (CAD) (OR = 10.315, P = 0.010), and invasive mechanical ventilation (OR = 3.926, P = 0.020) emerged as significant predictors of mortality. In contrast, elevated C-reactive protein (CRP) (OR = 1.011, P = 0.003), procalcitonin (PCT) (OR = 1.030, P = 0.005), and lower hemoglobin levels (OR = 0.963, P = 0.004) were independently associated with SIC. The AUC of mortality prediction model is 0.908, while the SIC prediction model yielded an AUC of 0.817. The predictive models developed in this study demonstrate early identification of mortality rates and SIC risk in PA BSI patients, which may have the potential to guide timely therapeutic interventions and improve clinical outcomes in this high-risk population.

Systemic Coagulation Derangement as an Early Sign of Oxygenator Failure in Veno-Venous Extracorporeal Membrane Oxygenation (VV ECMO) Without Anticoagulation

Background and Clinical Significance: Veno-venous extracorporeal membrane oxygenation (VV ECMO) has become a widely accepted supportive treatment for severe acute respiratory distress syndrome (ARDS) in intensive care units (ICUs). Although it has gained popularity, some of its aspects, including optimal anticoagulation management and the best means of monitoring hemostasis, remain unresolved. Thrombosis and bleeding are still important complications of ECMO. Case Presentation: A 44-year-old male patient, with no underlying conditions, was diagnosed with severe acute respiratory distress syndrome (ARDS) due to AH1N1 influenza. He presented severe hypoxemia despite the use of mechanical ventilation, neuromuscular blocking agent infusion and prone position. VV ECMO was used, and coagulation was stopped on ECLS day 6 due to severe pulmonary hemorrhage. The systemic hemostatic disorders found in this patient were difficult to differentiate from disseminated intravascular coagulation (DIC) or sepsis-induced coagulopathy (SIC), improved transiently after circuit exchange, and resolved only after discontinuation of ECMO. The patient was discharged fully conscious and cooperative, with no apparent neurological deficit. Conclusions: Systemic hemostatic abnormalities may precede oxygenator failure and mimic DIC or SIC. Timely oxygenator exchange may therefore be considered. However, it is a high-risk procedure, especially in fully ECLS-dependent patients.

Association between liver fibrosis and the in-hospital mortality in patients with sepsis-induced coagulopathy

BackgroundThe impact of liver fibrosis on the clinical outcomes of patients with sepsis-induced coagulopathy (SIC) is not well understood. This study aimed to evaluate the association between liver fibrosis scores and in-hospital mortality in SIC patients.MethodsIn this retrospective observational cohort study, data were collected from patients diagnosed with sepsis and admitted to the ICU at the First Affiliated Hospital of Wenzhou Medical University between January 2017 and December 2023. Liver fibrosis was evaluated using three scores: Fibrosis-4 (Fib-4), Aspartate Aminotransferase–to–Platelet Ratio Index (APRI), and Nonalcoholic Fatty Liver Disease Fibrosis Score (NFS). Patients were divided into tertiles according to their liver fibrosis scores, and the primary outcome was in-hospital mortality. Multivariable logistic regression and restricted cubic spline regression analyses were used to assess associations, complemented by sensitivity analyses through subgroup evaluations.ResultsThe cohort included 948 patients diagnosed with SIC with an in-hospital mortality of 26.16%. Multivariate logistic regression analysis revealed a significant association between higher liver fibrosis scores and increased in-hospital mortality. Specifically, patients in the highest tertile of Fib-4, APRI, and NFS scores had significantly higher odds of mortality (FIB-4: OR 3.62, 95% CI 1.03–12.69; APRI: OR 2.16, 95% CI 0.88–5.30; NFS: OR 6.80, 95% CI 2.11–21.93) compared to those in the lowest tertile. The restricted cubic spline regression model showed a linear increase in the risk of in-hospital mortality with increasing liver fibrosis score. Sensitivity analysis confirmed the consistency and stability of the results across the different subgroups.ConclusionOur study suggests that elevated liver fibrosis scores, particularly Fib-4 and NFS, are associated with higher in-hospital mortality in SIC patients. Further research, especially larger prospective studies, are needed to validate these findings.

Heparin-binding protein and sepsis-induced coagulopathy: Modulation of coagulation and fibrinolysis via the TGF-β signalling pathway

BackgroundHeparin-binding protein (HBP) levels have been linked to organ failure and may represent an inflammatory biomarker of sepsis. We found disseminated intravascular coagulation (DIC) is associated with higher HBP levels in patients and in in vivo and in vitro models. This prospective, single-center observational study investigated the effects and underlying mechanisms of HBP on the coagulation cascade in sepsis. Methods538 patients with sepsis from June 2016 to December 2019 were enrolled. Mechanisms underlying HBP and the coagulation system were investigated in human umbilical vein endothelial cells (HUVEC) and C57 mice. ResultsIncreased HBP was associated with sepsis-induced DIC. The optimal cutoff value was 37.5 ng/mL (sensitivity: 56 %, specificity: 65 %). Antithrombin-III (AT-III) activity, plasmin-a2 plasmin inhibitor complex (PIC), procalcitonin (PCT), hemoglobin, and HBP ≥37.5 ng/mL were associated with of DIC occurrence. In HUVECs &C57 mice models, Western blotting, qPCR, and immunohistochemistry analysis showed that the binding between HBP and TGF-β receptor 2 (TGFBR2) caused elevation of plasminogen activator inhibitor-1 (PAI-1) levels. Furthermore, we found that mice stimulated with HBP had higher levels of fibrinogen and D-dimer in the blood. HBP treatment caused the accumulation of fibrinogen in mice lung tissue. Treatment with TGFBR2-small interfering RNAs inhibited the effects. ConclusionPatients with sepsis having HBP ≥37.5 ng/mL at admission were more likely to develop DIC. HBP upregulates the expression of fibrinogen and PAI-1 via TGFBR2 and the TGF-β signalling pathway.

Extracellular vesicle tissue factor and tissue factor pathway inhibitor are independent discriminators of sepsis-induced coagulopathy

BackgroundSepsis-induced disseminated intravascular coagulopathy (DIC) remains a challenging clinical entity associated with significant morbidity and mortality. Endothelial injury or activation and extracellular vesicles (EV) are postulated as important determinants of DIC. However, there is limited research available which specifically tests the discriminatory ability of these characteristics in sepsis-induced coagulopathy. MethodsIn this prospective, single-centre study we collected plasma samples within 24 hours after sepsis diagnosis and followed these patients for five consecutive days. Overt DIC was determined by the ISTH-DIC score. 87 sepsis patients were recruited (35 with overt DIC) and presented with increased levels of EV, EV-associated TF activity (TF-PCA), E-selectin, TF and TFPI at admission compared to healthy subjects. ResultsOnly TFPI levels and TF-PCA discriminated between sepsis patients with or without DIC (AUC 0.76, p = 0.0002). Increased TF-PCA was not sensitive in detecting sepsis-associated DIC, however levels above 1.38 pg/mL showed a high specificity in this cohort (sensitivity 27%, specificity 95%). The hazard ratio to progress to DIC over five days was 1.14 (95% CI 0.64 – 2.07) for TF-PCA levels of 0.5 pg/mL or higher and 3.18 (95% CI 1.74 – 5.79) for TFPI levels of 22.28 ng/mL or higher at admission. ConclusionThese findings highlight the critical balance between pro- and anticoagulant factors, especially the pivotal roles of TF-PCA and TFPI in an early phase of sepsis-induced DIC. Only EV-associated and functionally active TF and not TF antigen levels showed a predictive potential regarding DIC. These novel results might support the improvement of diagnostic or even therapeutic strategies to mitigate the devastating consequences of DIC in septic patients.

Novel nomogram for the prediction of sepsis-induced coagulopathy in the PICU: A multicentre retrospective study

IntroductionSepsis-induced coagulopathy (SIC) is a severe complication of sepsis, characterized by poor prognosis and high mortality. However, the predictors of SIC in pediatric patients have yet to be identified. Our aim was to develop a user-friendly and efficient nomogram for predicting SIC in sepsis patients admitted to the pediatric intensive care unit (PICU). Materials and methodsWe screened 948 sepsis patients admitted to the PICU in three hospitals located in Shandong, China. Least absolute shrinkage and selector operation (LASSO) regression was used in the training cohort for variable selection and regularization. The selected variables were utilized to construct a nomogram for predicting the risk of SIC among sepsis patients admitted to the PICU. ResultsOverall, SIC was observed in 324 (40.3 %) patients. The morbidity of SIC in sepsis patients is associated with age, fibrinogen, prothrombin time, C-reactive protein, lactate and the pediatric sequential organ failure assessment score. We developed a nomogram for the early identification of SIC in the training cohort (area under the curve [AUC] 0.869, 95 % confidence interval [CI] 0.830–0.907, sensitivity 75.7 %, specificity 84.8 %) and validation cohorts (validation cohort 1: AUC 0.854, 95 % CI 0.805–0.903, sensitivity 72.0 %, specificity 86.9 %; validation cohort 2: AUC 0.853, 95 % CI 0.796–0.910, sensitivity 70.1 %, specificity 87.8 %). The calibration plots of the nomogram demonstrated a high level of concordance in the SIC probabilities between the observed and predicted values. ConclusionsThe novel nomogram showed excellent predictive performance for the morbidity of SIC among sepsis patients admitted to the PICU, potentially assisting healthcare professionals in early identification and intervention for SIC.

Elevated level of extracellular vimentin is associated with an increased fibrin formation potential in sepsis: ex vivo swine study

BackgroundSepsis can lead to coagulopathy and microvascular thrombosis. Prior studies, including ours, reported an increased level of extracellular vimentin in blood derived from septic patients. Moreover, we identified the contribution of extracellular vimentin to fibrin formation and to the fibrin clot structure ex vivo in plasma from septic patients. Here, we tested the status of plasma vimentin and its impact on fibrin clots using our recently described swine model of methicillin-resistant Staphylococcus aureus (MRSA) sepsis-induced coagulopathy.ResultsWe employed ELISA, size-exclusion chromatography, vimentin antibodies, confocal microscopy, and turbidity assays on piglet plasma obtained at pre- and post-MRSA inoculation. Plasma vimentin level at 70 h post-MRSA inoculation was on average twofold higher compared to pre-infection (0 h) level in the same animal. Anti-vimentin antibody effectively reduced fibrin formation ex vivo and increased porosity in the fibrin clot structure generated from septic piglet plasma. In contrast to plasma at 0 h, the size-exclusion chromatography revealed that phosphorylated vimentin was in-complex with fibrinogen in septic piglet plasma.ConclusionsThus, our swine model of sepsis-induced coagulopathy, reproduced increased extracellular circulating vimentin and subsequent potentiation of fibrin formation, often observed in septic patient. These outcomes validate the use of large animal models to investigate the dysregulated host immune response to infection leading to coagulopathy, and to develop new therapies for sepsis-induced disseminated microvascular thrombosis.

The Nonlinear Relationship Between Temperature and Prognosis in Sepsis-induced Coagulopathy Patients: A Retrospective Cohort Study from MIMIC-IV Database.

The prognostic value of body temperature in sepsis-induced coagulopathy (SIC) remains unclear. In this study we aimed to investigate the association between temperature and mortality among SIC patients. We analyzed data for 9,860 SIC patients from an intensive care database. Patients were categorized by maximum temperature in the first 24 hours into the following: ≤36.0°C; 36.0-37.0°C; 37.0-38.0°C; 38.0-39.0°C; and ≥39.0°C. The primary outcome was 28-day mortality. We used multivariate regression to analyze the temperature-mortality association. The 37.0-38.0°C, 38.0-39.0°C and ≥39.0°C groups correlated with lower 28-day mortality (adjusted HR 0.70, 0.76 and 0.72, respectively), while the <36.0°C group correlated with higher mortality compared to the 36.0-37.0°C group (adjusted HR 2.60). A nonlinear relationship was observed between temperature and mortality. Subgroup analysis found no effect modification except in cerebrovascular disease. A body temperature in the range of 37.0-38.0°C was associated with a significantly lower mortality compared to the normal temperature (36.0-37.0°C) group. Additionally, a gradual but statistically insignificant increase in mortality risk was observed when body temperature exceeded 38.0°C. Further research should validate these findings and elucidate involved mechanisms, especially in cerebrovascular disease subgroups.

Study of Various Disseminated Intravascular Coagulation Scores and Sequential Organ Failure Assessment Score in Medical Intensive Care Unit.

Aim The aim of the present study was to assess the disseminated intravascular coagulation (DIC) and its correlation with DIC scores (International Society on Thrombosis and Haemostasis (ISTH), sepsis-induced coagulopathy (SIC)) and Sequential Organ Failure Assessment (SOFA) score in medical intensive care unit (MICU) patients. Methods The study was conducted at the medical intensive care unit at Dr. D.Y. Patil Medical College and Hospital, D.Y. Patil Vidyapeeth, Pimpri, Pune spanning from October 2020 to September 2022. A total of 100 patients admitted to the hospital ICU satisfying qSOFA score were included in the current study. Approval was obtained from the institutional ethics committee before commencing the study. All patients and their family members included in the study were provided with a detailed explanation of the study. Clinical history of illness and physical examination were done in detail. The laboratory values were obtained and were calculated with the International Society on Thrombosis and Haemostasis (ISTH), sepsis-induced coagulopathy (SIC) and Sequential Organ Failure Assessment (SOFA) scores. Results The average age of the study population was 52.08 ± 16.44 years. Within the study population, 65% were male and 35% were female. Within the group being studied, the average pulse rate was 66.64 ± 17.33 beats per minute, the average systolic blood pressure was 83.7 ± 11.38 mm Hg, the average diastolic blood pressure was 59.7 ± 10.49 mm Hg, and the average respiratory rate was 38.4 ± 4.8. The average Glasgow Coma Scale (GCS) among the participants was 9.51 ± 1.74. The average qSOFA score across the study participants was 2.58 ± 0.6. The study population consisted of 60% survivors and 40% non-survivors. Regarding the study population, 57.15% of individuals experienced mortality as a result of DIC. The statistical analysis revealed a significant difference in the mean ISTH score between the result groups at 48 hours. The disparity in the average SOFA score at admission, 24 hours, 48 hours, day 7 and day 14 between the outcomes (survivors and non-survivors) was statistically significant. Conclusion This research suggests that there is a positive link between higher scores on the estimated ISTH, SIC and SOFA scales. The prognosis of critically sick patients is negatively correlated with the progressive increase in DIC scores throughout follow-up, while a stable or declining DIC score is indicative of a more favorable prognosis. There was no significant link seen between non-overt disseminated intravascular coagulation (DIC) mortality and DIC scores.

Association between the use of statins and in-hospital mortality risk in patients with sepsis-induced coagulopathy during ICU stays: a study based on medical information mart for intensive care database

BackgroundThe objective of this study was to explore the correlation between statin administration in the intensive care unit (ICU) setting and the in-hospital mortality risk of patients suffering from sepsis-induced coagulopathy (SIC).MethodsUtilizing a retrospective cohort study design, this investigation collected data from the Medical Information Mart for Intensive Care (MIMIC)-IV spanning 2008 to 2019. The diagnosis of SIC was established based on a SIC score of 4 or above. Statin usage during the ICU period was extracted from the prescription records based on the keywords of statin medications. The primary endpoint analyzed was the in-hospital mortality within the ICU, characterized by any death occurring during the ICU admission.ResultsDuring the follow-up, which had a median duration of approximately 7.28 days, 18.19% of the 4,777 SIC patients died in the ICU. Statin was linked with a decrease in the risk of in-hospital mortality for SIC patients in the ICU [hazard ratio (HR): 0.73, 95% confidence interval (CI): 0.60–0.89, P = 0.002]. Relative to rosuvastatin, the use of atorvastatin (HR: 0.54, 95% CI: 0.34–0.85, P = 0.008) or simvastatin (HR: 0.55, 95% CI: 0.33–0.92, P = 0.024), as well as combinations of multiple statins (HR: 0.36, 95% CI: 0.15–0.86, P = 0.022), was associated with a reduction in ICU in-hospital mortality risk. Subgroup analysis also suggested that the use of atorvastatin, simvastatin, or a combination of statins had an advantage over rosuvastatin in reducing ICU in-hospital mortality in SIC patients older than 65 years of age or SIC patients with respiratory failure or cardiogenic shock (all P < 0.05).ConclusionThe present study supports the potential benefits of statin use in mortality in SIC patients during ICU stays. The study encourages clinicians to consider the benefits of statins and supports the ongoing exploration of statins for enhanced outcomes in critical care settings.

The relationship between dexmedetomidine administration and prognosis in patients with sepsis-induced coagulopathy: a retrospective cohort study.

Background: This study aimed to investigate whether dexmedetomidine provides survival benefit in critically ill patients with sepsis-induced coagulopathy (SIC). Methods: Patients with sepsis-induced coagulopathy admitted to the ICU were identified from the Medical Information Marketplace for Intensive Care (MIMIC)-IV database. They were divided into two groups: patients who started dexmedetomidine within 48h of ICU admission and lasted for more than 4h and patients who did not receive dexmedetomidine as a control group. The primary outcome was 28-day hospital mortality, the secondary outcome was in-hospital mortality, and the extended outcomes included duration of mechanical ventilation and vasopressor use, ICU stay, and hospital stay. Propensity score matching (PSM) analysis was used to match patients who received dexmedetomidine with those who did not, and multivariable Cox models and logistics models were used to account for baseline differences and unmeasured confounders. An external validation was performed with the Critical care database comprising patients with infection at Zigong Fourth People's Hospital. Results: After PSM, 592 patients who received dexmedetomidine were matched with 592 patients who did not receive dexmedetomidine. In the primary and secondary endpoints, dexmedetomidine was associated with a lower risk of 28-day hospital mortality (19.3% vs. 14.2%, hazard ratio (HR) 0.71; P = 0.020) and in-hospital mortality (22.3% vs. 16.4%, odds ratio (OR) 0.68; P = 0.017) in patients with SIC. Regarding the extended outcome, dexmedetomidine was also associated with a longer length of hospital stay (median 12.54days vs. 14.87days, P = 0.002) and longer ICU stay (median 5.10days vs. 6.22days, P = 0.009). In addition, the duration of mechanical ventilation was significantly increased in the dexmedetomidine group (median 41.62h vs. 48.00h, p = 0.022), while the duration of vasopressor use was not significantly different (median 36.67h vs. 39.25h, p = 0.194). Within 48h of ICU stay, receiving a dose of dexmedetomidine greater than 0.474μg/kg/h and continuous dexmedetomidine administration for 24-48h may be associated with 28-day hospitalization outcomes in patients with SIC. External cohort validation also found that the use of dexmedetomidine after admission to the ICU can reduce 28-day mortality in patients with SIC. Conclusion: Dexmedetomidine administration is associated with reduced 28-day hospital mortality and in-hospital mortality in critically ill patients with SIC, and these findings deserve further verification in randomized controlled trials.

Development and Validation of a Nomogram for Predicting Sepsis-Induced Coagulopathy in Septic Patients: Mixed Retrospective and Prospective Cohort Study.

Sepsis-induced coagulopathy (SIC) is a common cause of poor prognosis in critically ill patients in the intensive care unit (ICU). However, currently there are no tools specifically designed for predicting the occurrence of SIC in septic patients earlier. This study aimed to develop a predictive nomogram incorporating clinical markers and scoring systems to individually predict the probability of SIC in septic patients. Patients consecutively recruited in the stage between January 2022 and April 2023 constituted the development cohort for retrospective analysis to internally test the nomogram, and patients in the stage between May 2023 to November 2023 constituted the validation cohort for prospective analysis to externally validate the nomogram. Univariate logistic regression analysis of the development cohort was performed firstly, and then multivariate logistic regression analysis was performed using backward stepwise method to determine the best-fitting model and obtain the nomogram from it. The nomogram was validated in an independent external validation cohort, involving discrimination and calibration. A decision curve analysis was also performed to evaluate the net benefit of the insertion decision with this nomogram. A total of 548 and 245 patients, 55.1 and 49.4% with SIC occurrence, were included in the development and validation cohorts, respectively. Predictors contained in the prediction nomogram included shock, platelets, and international normalized ratio (INR). Patients with shock (odds ratio [OR]: 4.499; 95% confidence interval [CI]: 2.730-7.414; p < 0.001), higher INR (OR: 349.384; 95% CI: 62.337-1958.221; p < 0.001), and lower platelet (OR: 0.985; 95% CI: 0.982-0.988; p < 0.001) had higher probabilities of SIC. The development model showed good discrimination, with an area under the receiver operating characteristic curve (AUROC) of 0.879 (95% CI: 0.850-0.908) and good calibration. Application of the nomogram in the validation cohort also gave good discrimination with an AUROC of 0.872 (95% CI: 0.826-0.917) and good calibration. The decision curve analysis of the nomogram provided better net benefit than the alternate options (intervention or no intervention). By incorporating shock, platelets, and INR in the model, this useful nomogram could be accessibly utilized to predict SIC occurrence in septic patients. However, external validation is still required for further generalizability improvement of this nomogram.

Efficacy of unfractionated heparin in patients with moderate sepsis-induced coagulopathy: An observational study

IntroductionThe 2021 Surviving Sepsis Campaign guidelines recommend low-molecular-weight heparin for the prevention of venous thromboembolism in sepsis. However, observational studies suggest that anticoagulants as a whole may benefit severely ill sepsis patients with coagulopathy, but the optimal targets of unfractionated heparin remain unclear. This study investigated which sepsis patients could most benefit from unfractionated heparin. Materials and methodsIn this retrospective observational study, we identified adult sepsis patients requiring urgent hospitalization from 2006 to 2019 using a large-scale Japanese medical database. Patients were divided into two groups: those receiving unfractionated heparin within 72 h of admission and those who did not. We compared in-hospital mortality, major bleeding complications, and thromboembolic events between these groups using a multivariate logistic regression model adjusted for patient and treatment variables. Additionally, we assessed the association between heparin administration and in-hospital mortality across various subgroups. ResultsAmong 30,342 sepsis patients, 2520 received early heparin administration, and 27,822 did not. Multivariate logistic regression revealed a significant association between heparin and reduced in-hospital mortality (adjusted OR: 0.735, 95 % CI: 0.596–0.903) but no significant association with major bleeding and thromboembolic risk (adjusted OR: 1.137, 1.243; 95 % CI: 0.926–1.391, 0.853–1.788, respectively). Subgroup analyses suggested significant survival benefits associated with heparin only in the sepsis patients with moderate coagulopathy and sepsis-induced coagulopathy scores of 3 or 4 (adjusted OR: 0.452, 0.625; 95 % CI: 0.265–0.751, 0.410–0.940, respectively). ConclusionsEarly heparin administration upon admission is associated with lower in-hospital mortality, especially in moderate sepsis-induced coagulopathy, and no significant increase in complications.

Sepsis-induced coagulopathy: a matter of timeline.

Sepsis-induced coagulopathy: a matter of timeline.

Vitamin K Prescribing Trends Among Critically Ill Children Hospitalized for Sepsis: A Multicenter Observational Cohort Study.

Objective: Vitamin K (VK) is commonly prescribed for pediatric sepsis-induced coagulopathy without trial-derived evidence to support its use for this indication. The purpose of this study was to characterize national prescribing trends for VK in this population. Patients and Methods: This is a multicenter retrospective cohort study using the Pediatric Health Information System registry including children 0 to 17 years of age hospitalized for sepsis in the pediatric intensive care unit from January 2016 through December 2022. The primary outcome was overall, annual, and center-specific VK prescribing rates. Descriptive data included demographics, length of stay, and rates of VK deficiency, hepatic insufficiency, red blood cell (RBC) transfusion, venous thromboembolism (VTE), and mortality. VK prescribing trends were assessed using Joinpoint regression. Descriptive statistics employed included Wilcoxon rank-sum, student's t, and chi-square tests. Results: Of the 31 221 encounters studied, 4539 (14.6%) were prescribed VK (median center-specific rate: 14.2%; interquartile range [IQR]: 8.8-21%) with a linear annual trend decreasing from 17.3% in 2016 to 13.3% in 2022 (-0.6%/year, r2 = .661). Those prescribed VK had greater rates of hepatic dysfunction (20.5% vs 3.1%), RBC transfusion (26.5% vs 11.2%), VTE (12.5% vs 4.6%), mortality (17.1% vs 4.4%), and median length of stay (16 [IQR: 8-33] vs 8 [4-15] days) (all P < .001). VK deficiency was diagnosed in 0.2% of encounters. Conclusions: In this multicenter retrospective cohort, VK prescribing was common among critically ill children diagnosed with sepsis. Phased trials are needed to demonstrate clinical efficacy and safety for VK in this population.

Prognostic gene landscapes and therapeutic insights in sepsis-induced coagulopathy

BackgroundSepsis is a common and critical condition encountered in clinical practice that can lead to multi-organ dysfunction. Sepsis-induced coagulopathy (SIC) significantly affects patient outcomes. However, the precise mechanisms remain unclear, making the identification of effective prognostic and therapeutic targets imperative. MethodsThe analysis of transcriptome data from the whole blood of sepsis patients, facilitated the identification of key genes implicated in coagulation. Then we developed a prognostic model and a nomogram to predict patient survival. Consensus clustering classified sepsis patients into three subgroups for comparative analysis of immune function and immune cell infiltration. Single-cell sequencing elucidated alterations in intercellular communication between platelets and immune cells in sepsis, as well as the role of the coagulation-related gene FYN. Real-time quantitative PCR determined the mRNA levels of critical coagulation genes in septic rats' blood. Finally, administration of a FYN agonist to septic rats was observed for its effects on coagulation functions and survival. ResultsThis study identified four pivotal genes—CFD, FYN, ITGAM, and VSIG4—as significant predictors of survival in patients with sepsis. Among them, CFD, FYN, and ITGAM were underexpressed, while VSIG4 was upregulated in patients with sepsis. Moreover, a nomogram that incorporates the coagulation-related genes (CoRGs) risk score with clinical features of patients accurately predicted survival probabilities. Subgroup analysis of CoRGs expression delineated three molecular sepsis subtypes, each with distinct prognoses and immune profiles. Single-cell sequencing shed light on heightened communication between platelets and monocytes, T cells, and plasmacytoid dendritic cells, alongside reduced interactions with neutrophils in sepsis. The collagen signaling pathway was found to be essential in this dynamic. FYN may affect platelet function by modulating factors such as ELF1, PTCRA, and RASGRP2. The administration of the FYN agonist can effectively improve coagulation dysfunction and survival in septic rats. ConclusionsThe research identifies CoRGs as crucial prognostic markers for sepsis, highlighting the FYN gene's central role in coagulation disorders associated with the condition and suggesting novel therapeutic intervention strategies.

Persistent high sepsis-induced coagulopathy and sequential organ failure assessment scores can predict the 28-day mortality of patients with sepsis: A prospective study

BackgroundThe performance of the sepsis-induced coagulopathy (SIC) and sequential organ failure assessment (SOFA) scores in predicting the prognoses of patients with sepsis has been validated. This study aimed to investigate the time course of SIC and SOFA scores and their association with outcomes in patients with sepsis.MethodsThis prospective study enrolled 209 patients with sepsis admitted to the emergency department. The SIC and SOFA scores of the patients were assessed on days 1, 2, and 4. Patients were categorized into survivor or non-survivor groups based on their 28-day survival. We conducted a generalized estimating equation analysis to evaluate the time course of SIC and SOFA scores and the corresponding differences between the two groups. The predictive value of SIC and SOFA scores at different time points for sepsis prognosis was evaluated.ResultsIn the non-survivor group, SIC and SOFA scores gradually increased during the first 4 days (P < 0.05). In the survivor group, the SIC and SOFA scores on day 2 were significantly higher than those on day 1 (P < 0.05); however, they decreased on day 4, dropping below the levels observed on day 1 (P < 0.05). The non-survivors showed higher SIC scores on days 2 (P < 0.05) and 4 (P < 0.001) than the survivors, whereas no significant differences were found between the two groups on day 1 (P > 0.05). The performance of SIC scores on day 4 for predicting mortality was more accurate than that on day 2, with areas under the curve of 0.749 (95% confidence interval [CI]: 0.674–0.823), and 0.601 (95% CI: 0.524–0.679), respectively. The SIC scores demonstrated comparable predictive accuracy for 28-day mortality to the SOFA scores on days 2 and 4. Cox proportional hazards models indicated that SIC on day 4 (hazard ratio [HR] = 3.736; 95% CI: 2.025–6.891) was an independent risk factor for 28-day mortality.ConclusionsThe time course of SIC and SOFA scores differed between surviving and non-surviving patients with sepsis, and persistent high SIC and SOFA scores can predict 28-day mortality.

COMPREHENSIVE THERAPEUTIC EFFICACY ANALYSIS OF INTRAVENOUS IMMUNOGLOBULIN IN TREATING SEPSIS-INDUCED COAGULOPATHY: A SINGLE-CENTER, RETROSPECTIVE OBSERVATIONAL STUDY.

Objective : The aim of the study is to investigate the efficacy of intravenous immunoglobulin (IVIg) in treating sepsis-induced coagulopathy ( SIC ). Methods : A retrospective controlled analysis was conducted on 230 patients with SIC at Ganzhou People's Hospital from January 2016 to December 2022. All patients were screened using propensity score matching and treated according to the SSC2016 guidelines. Compared with the control group (n = 115), patients in the test group (n = 115) received IVIg (200 mg/kg.d) for 3 consecutive days after admission. The rating scales, coagulation function, survival, and treatment duration were evaluated. Results : On day 3 of treatment, both groups exhibited reduced platelet and thromboelastogram (TEG) maximum amplitude (MA) levels, with the control group showing a more significant decrease ( P < 0.05). By the fifth day, these levels had recovered in both groups. However, the test group experienced a significant increase by day 7 ( P < 0.05). Coagulation factors II and X began to increase on day 3, and normalization was significantly faster in the test group on day 5 ( P < 0.05). The levels of prothrombin time, international normalized ratio, activated partial thromboplastin time, d -dimer, fibrinogen, fibrin degradation products, TEG-R, and TEG-K exhibited a notable decline on day 3 and demonstrated significantly faster recovery on day 5 in the test group ( P < 0.05). In addition, both groups showed a reduction in Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment, disseminated intravascular coagulation, and lactate (LAC) levels on day 3, but the test group's scores decreased significantly more by day 7 ( P < 0.05). Within the test group, white blood cell count, C-reactive protein, procalcitonin, IL-6, and Tmax levels were lower ( P < 0.05). Furthermore, the test group demonstrated shorter duration for intensive care unit stay, mechanical ventilation, and continuous renal replacement therapy ( P < 0.05). No significant differences were observed in the duration of fever or vasoactive drug use between the groups. However, the log-rank method indicated a higher 28-day survival rate in the test group ( P < 0.05). Conclusion : IVIg can successfully increase platelet count and coagulation factors, correct coagulation disorders, enhance organ function, and reduce 28-day mortality in patients with SIC .

Comparison of Three Different Disseminated Intravascular Coagulation (DIC) Criteria and Diagnostic and Prognostic Value of Antithrombin Investigation in Patients with Confirmed Sepsis-Induced Coagulopathy (SIC).

A new scoring system termed sepsis-induced coagulopathy (SIC) has been proposed to diagnose early sepsis-induced disseminated intravascular coagulation (DIC). This study performed DIC-related analyses in patients with confirmed SIC. Data from the intensive care unit (ICU) departments of the three hospitals between 2020 and 2022 were retrospectively analyzed. Finally, 125 patients with confirmed SIC were enrolled in the study. The diagnostic value of three widely used DIC criteria was assessed in patients with newly diagnosed SIC. In addition, the diagnostic and prognostic value of antithrombin (AT) was analyzed in patients with SIC. The Japanese Association for Acute Medicine DIC criteria (JAAM) exhibited the highest DIC diagnostic rate, while the mortality risk of SIC patients demonstrated a proportional increase with higher International Society on Thrombosis and Haemostasis (ISTH) and Chinese DIC scoring system (CDSS) scores. Low AT activity (<70%) in septic patients upon SIC diagnosis predicted a very high 28-day mortality rate, almost twice as high as in the normal AT activity (≥70%) group. A decreasing tendency in AT activity after clinical interventions was correlated with increased mortality. The area under the ROC curve (AU-ROC) of AT in DIC diagnosis was statistically significant when CDSS and ISTH were used as diagnostic criteria, but not JAAM. Each of the three DIC diagnostic criteria showed diagnostic and prognostic advantages for SIC. AT could be an independent prognostic indicator for SIC but demonstrated a relatively limited DIC diagnostic value. Adding AT to the SIC scoring system may increase its prognostic power.

Relationship between serum sodium level and sepsis-induced coagulopathy.

A discussion about the correlation between the level of serum sodium and sepsis-induced coagulopathy (SIC). A retrospective analysis was conducted on sepsis patients who were admitted to the Intensive Care Unit (ICU) of Nanjing Drum Tower Hospital from January 2021 to December 2022. Based on the presence of coagulation disorders, the patients were divided into two groups: sepsis-induced coagulopathy (SIC) and non-sepsis-induced coagulopathy (non-SIC) groups. We recorded demographic characteristics and laboratory indicators at the time of ICU admission, and analyzed relationship between serum sodium level and SIC. One hundred and twenty-five patients with sepsis were enrolled, among which, the SIC and the non-SIC groups included 62 and 63 patients, respectively. Compared to patients in the non-SIC group, the level of serum sodium of those in the SIC was significantly higher (p < 0.001). Multi-factor logistic regression showed serum sodium level was independently associated with SIC (or = 1.127, p = 0.001). Pearson's correlation analysis indicated that the higher the serum sodium level, the significantly higher the SIC score was (r = 0.373, p < 0.001). Additionally, the mortality rate of patients with sepsis in the ICU were significantly correlated with increased serum sodium levels (p = 0.014). An increase in serum sodium level was independently associated with an increased occurrence of SIC and also associated with the poor prognosis for patients with sepsis.