Biomarkers of sepsis-induced coagulopathy: diagnostic insights and potential therapeutic implications

Annals of Intensive Care, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 17, 2025

Diagnosing coagulopathy in septic patients remains challenging intensive care. Disseminated intravascular coagulation (DIC) indeed presents with complex pathophysiology, complicating timely diagnosis. Epidemiological data indicate a significant prevalence of DIC patients, mortality rates up to 60%. Despite advances, current biomarker-based diagnostic tools often fail provide early and accurate detection. This review evaluates the utility limitations traditional emerging biomarkers for diagnosing sepsis-induced (SIC) DIC. We also assess effectiveness anticoagulant therapy guided by criteria.

Язык: Английский

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Thrombocytopenia in Critically Ill Children: A Review for Practicing Clinicians

Children, Год журнала: 2025, Номер 12(1), С. 83 - 83

Опубликована: Янв. 12, 2025

Thrombocytopenia frequently occurs in patients before, during, and after admission to Pediatric Intensive Care Units (PICUs). In critically ill children, it is often due multifactorial causes can be a sign of significant organ dysfunction. This review summarizes the potential causes/mechanisms thrombocytopenia acutely their identification, treatments, with special attention paid septic patients. The mechanisms include decreased production sequestration, but most common reason increased destruction or consumption. specifically reviews compares presentation, pathogenesis, treatment disseminated intravascular coagulation (DIC) thrombotic microangiopathic spectrum (TMA), including thrombocytopenia-associated multiorgan failure (TAMOF), hemolytic uremic syndrome, other diagnoses. etiologies discussed HLH/MAS, immune thrombocytopenia, dilutional thrombocytopenia. Finally, this analyzes platelet transfusions, various thresholds, complications.

Язык: Английский

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Plasma EphA2 level is a superior biomarker to Del-1 for sepsis diagnosis and prognosis

Frontiers in Medicine, Год журнала: 2025, Номер 12

Опубликована: Янв. 24, 2025

Background Sepsis, characterized by a dysregulated host response to infection, often leads organ dysfunction, and vascular endothelial dysfunction plays central role. The erythropoietin-producing hepatocellular carcinoma (Eph)A2 receptor is associated with increased permeability; however, the developmental locus-1 (Del-1), has contrasting effects on function. Hence, we examined their potential as biomarkers of sepsis. Methods In total, 117 participants, including 20 healthy controls, 21 patients systemic inflammatory syndrome (SIRS), 76 sepsis, were enrolled in this study. Sepsis severity was assessed using Acute Physiology Chronic Health Evaluation (APACHE) II Sequential Organ Failure Assessment (SOFA) scores. Results Median plasma EphA2 levels progressively from controls SIRS sepsis cases (154.29, 293.52, 554.24 pg/mL; all p < 0.05). median Del-1 highest lowest SIRS, intermediate level (101.27, 16.88, 36.9 0.001). both higher 28-day non-survivors than survivors, (EphA2:898.09 vs. 475.88 pg/mL, 0.001; Del-1:46.09 32.68 = 0.193); only statistically significant. area under curve for 0.74 receiver operating characteristic analysis predicting mortality, whereas APACHE II, SOFA, showed values 0.762, 0.614, 0.595, respectively. Kaplan–Meier these cutoffs revealed that survival significantly group low compared high markers ( Conclusion Plasma consistently severity, suggesting its biomarker value diagnosis prognosis. contrast, variable, indicating limited prognostic utility.

Язык: Английский

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The diagnosis of DIC: a current overview

Frontiers in Medicine, Год журнала: 2025, Номер 12

Опубликована: Янв. 31, 2025

The name of disseminated intravascular coagulation (DIC) and its diagnostic criteria remain controversial. DIC is a clinical syndrome caused by variety etiologies, which determines high heterogeneity. It inappropriate to adopt the same criteria. has common characteristics. First, in most DIC, thrombosis bleeding coexist. Second, dynamic process. Third, endothelial cell injury systemic activation are core DIC. Fourth, an initiating factor multiple organ dysfunction (MODS). There still controversies about it relies on manifestations laboratory tests, cannot reflect pathophysiology. were not sensitive or specific. there lack biomarkers. parameters current fully actual function. Fifth, obviously use scoring system for diagnosis syndromes with different etiologies Therefore, urgent re-establish In recent years, understanding been continuously improved, including in-depth pathogenesis, classification phenotypes, development "two-step" etc. All these contribute establishment new conclusion, necessary develop personalized based etiology, reflecting pathophysiological mechanisms, establishing clear cut-off values parameters, being applicable, globally unified, importantly, able identify therapeutic targets.

Язык: Английский

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S100A4 participates in sepsis-induced endothelial cell inflammatory response and barrier damage by binding to BRD4

Clinical Hemorheology and Microcirculation, Год журнала: 2025, Номер unknown

Опубликована: Фев. 18, 2025

Background Research has shown that S100A4 is upregulated in endothelial cells when exposed to serum from septic patients. This article aims explore the role of endogenous lipopolysaccharide (LPS)-induced cells. Methods A HUVECs injury model was established using LPS and transfected with siRNA-S100A4 or Ov-BRD4 plasmid. Targets were predicted online databases, immunoprecipitation (IP) used verify binding targets. Cell viability, levels apoptosis, expression apoptosis-related proteins measured assess cell injury. Transendothelial electrical resistance (TER) tight junction barrier function. Assessed inflammatory response by measuring factors, adhesion THP-1 monocytes, molecules. Results Database prediction IP verification indicated could bind BRD4 LPS-induced HUVECs, increased HUVECs. Interference significantly enhanced viability TER, reduced TNFα, IL-1β, IL-6 levels, number LPS-treated Additionally, interference Bcl2, ZO-1, occludin, claudin-4 proteins, downregulated BRD4, Bax, cleaved caspase-3, ICAM-1, VCAM-1, E-selectin However, overexpression attenuated protective effect interfering on Conclusion involved damage BRD4.

Язык: Английский

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Sepsis: the evolution of molecular pathogenesis concepts and clinical management

MedComm, Год журнала: 2025, Номер 6(3)

Опубликована: Фев. 23, 2025

Abstract The mortality rate of sepsis is approximately 22.5%, accounting for 19.7% the total global mortality. Since Lewis Thomas proposed in 1972 that “it our response makes disease (sepsis)” rather than invading microorganisms, numerous drugs have been developed to suppress “overwhelming” inflammatory response, but none them has achieved desired effect. Continued failure led investigators question whether deaths septic patients are indeed caused by uncontrolled inflammation. Here, we review history clinical trials based on evolving concepts pathogenesis over past half century, summarize factors these historical and prerequisites success future drugs, propose basic principles preclinical research ensure successful translation. strategy targeting like attempting eliminate invaders suppressing host's armed forces, which logically untenable. Sepsis may not be complex; rather, result a fight microbes when force an pathogen overwhelms defenses. Thus, strengthening body's defense forces instead correct overcome sepsis.

Язык: Английский

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Biomarkers of cell cycle arrest, microcirculation dysfunction, and inflammation in the prediction of SA-AKI

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Март 7, 2025

Sepsis-associated acute kidney injury (SA-AKI) is a severe complication in critically ill patients, with complex pathogenesis involving cell cycle arrest, microcirculatory dysfunction, and inflammation. Current diagnostic strategies remain suboptimal. Therefore, this study aimed to evaluate pathophysiology-based biomarkers develop an improved predictive model for SA-AKI. The prospective observational was conducted, enrolling 26 healthy individuals 96 sepsis patients from Peking University Third Hospital. Clinical laboratory data were collected, monitored AKI development within 72 h. Further, categorized into SA-noAKI (n = 46) SA-AKI 50) groups. Novel biomarkers, including tissue inhibitor of metalloproteinase-2 (TIMP-2), insulin-like growth factor-binding protein-7 (IGFBP-7), angiopoietin-2 (Ang-2), measured all participants. Among these the incidence 52.08% (50/96). Compared SA-noAKI, group had significantly higher levels TIMP-2 (93.55 [79.36, 119.56] ng/mL), IGFBP-7 (27.8 [21.44, 37.29] TIMP-2×IGFBP-7 (2.91 [1.90, 3.55] (ng/mL)²/1000), Ang-2 (10.61 [5.79, 14.57] ng/mL) (P < 0.05). Accordingly, logistic regression identified (OR 2.71), 1.19), PCT 1.05) as independent risk factors. ROC curve demonstrated superior early-stage accuracy (AUC 0.898), which remained stable during internal validation 0.899). Meanwhile, nomogram exhibited that characterized excellent discrimination, calibration, clinical performance. In general, TIMP-2×IGFBP-7, factors SA-AKI, novel based on three indicators provided more accurate sensitive strategy early prediction

Язык: Английский

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Activated Notch1 promotes macrophage polarization and exacerbates sepsis-induced acute lung injury via β-catenin/NF-κB signaling

Biochemical Pharmacology, Год журнала: 2025, Номер unknown, С. 116892 - 116892

Опубликована: Март 1, 2025

Язык: Английский

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Relationship between coagulopathy score and survival in critically ill patients with liver cirrhosis and sepsis: a retrospective study

BMC Infectious Diseases, Год журнала: 2025, Номер 25(1)

Опубликована: Март 26, 2025

This research focused on exploring the association between coagulopathy scores and survival outcomes, both short-term long-term, in individuals diagnosed with liver cirrhosis complicated by sepsis. study retrospectively analyzed data from sepsis who were admitted to intensive care unit (ICU) at Beth Israel Deaconess Medical Center 2008 2022. The main outcome of interest was all-cause mortality within 28 days post-admission, while secondary assessed 90 days. We used Kaplan-Meier analysis compare risk among different groups. To evaluate relationship score patients sepsis, a multivariate Cox proportional hazards regression performed. predictive performance for short- long-term using receiver operating characteristic (ROC) curve analysis, which included evaluation its sensitivity, specificity, area under curve. Subgroup analyses performed across total 2,278 patients. demonstrated that elevated exhibited markedly higher rates ICU mortality, in-hospital as well 28-day 90-day all log-rank tests yielding P-values less than 0.001. results showed an independently linked before after controlling potential confounders. ROC although slightly prognosis Model End-stage Liver Disease score, it significantly outperformed Sequential Organ Failure Assessment Sepsis-induced Coagulopathy score. revealed no significant interaction subgroups. Higher critically ill associated poor prognosis. Due simplicity value, can serve effective complement existing clinical tools managing

Язык: Английский

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Protein C in adult patients with sepsis: from pathophysiology to monitoring and supplementation

Journal of Anesthesia Analgesia and Critical Care, Год журнала: 2025, Номер 5(1)

Опубликована: Апрель 14, 2025

Abstract Protein C (PC) plays a crucial role in modulating inflammation and coagulation sepsis. Its anticoagulant cytoprotective properties are critical mitigating sepsis-induced coagulopathy, which is associated with high mortality rates. In sepsis, low levels of PC an elevated risk multiple organ dysfunction increased mortality. Routine monitoring not widely implemented but appears relevant selected populations, such as patients purpura fulminans, coagulopathy (SIC), disseminated intravascular (DIC) or hyperinflammatory septic shock phenotypes. Treatment has been limited to concentrate approved for paediatric use congenital deficiencies while the efficacy supplementation sepsis remains subject debate. Considering physiological significance its pathophysiology, additional studies necessary fully elucidate therapeutic specific clinical settings.

Язык: Английский

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