Daily Sepsis Research Analysis
Analyzed 11 papers and selected 3 impactful papers.
Summary
The most impactful studies addressed sepsis-associated coagulopathy and mortality prediction using prospective biomarker cohorts, as well as context-specific risk stratification in children in a resource-limited setting. Particularly notable findings were the association of extracellular-vesicle tissue factor activity with disseminated intravascular coagulation, the prognostic value but limited diagnostic value of VWF/ADAMTS-13 ratios, and the strong sensitivity of the Lambaréné Organ Dysfunction Score in Tanzanian children.
Research Themes
- Sepsis-associated coagulopathy and extracellular-vesicle tissue factor biology
- Context-specific pediatric sepsis risk stratification
- VWF/ADAMTS-13 imbalance as a prognostic marker
Selected Articles
1. Circulating extracellular vesicle tissue factor activity is associated with disseminated intravascular coagulation in 2 cohorts of patients with sepsis.
This study evaluated extracellular-vesicle tissue factor activity in two sepsis cohorts, including longitudinal samples and patients who subsequently developed disseminated intravascular coagulation. Activity was associated with established disseminated intravascular coagulation in both cohorts, but it did not distinguish pre-DIC patients from those without DIC, indicating stronger value as a marker of ongoing coagulation activation than as an early predictive test.
Impact: The study links a mechanistically relevant coagulation mediator to sepsis-associated DIC using two independent patient cohorts and longitudinal sampling. Its negative finding in pre-DIC patients prevents overinterpretation and clarifies that the assay is not yet an established early-warning biomarker.
Clinical Implications: EV-TF activity may complement conventional coagulation testing when assessing established DIC in sepsis, but it should not currently replace standard scores or be used alone to predict imminent DIC. Clinical implementation requires assay standardization and prospective validation.
Key Findings
- EV-TF activity was higher in patients with sepsis than in healthy controls.
- EV-TF activity was associated with DIC in both the sequential and selected cohorts.
- EV-TF activity did not significantly distinguish pre-DIC patients from patients without DIC, and activity decreased over time in patients with DIC.
Methodological Strengths
- Use of two clinically distinct sepsis cohorts, including a longitudinal cohort and a cohort enriched for subsequent DIC development.
- Assessment against the updated 2025 International Society on Thrombosis and Haemostasis DIC score.
Limitations
- The EV-TF activity assay was an in-house assay, which may limit interlaboratory reproducibility.
- The study was observational and did not establish whether EV-TF activity is causally involved in DIC or improves clinical decision-making.
Future Directions: Future studies should standardize EV-TF assays, define sampling and timing protocols, and test whether serial EV-TF measurements add predictive or therapeutic value beyond established DIC scores and routine coagulation tests.
BACKGROUND: Disseminated intravascular coagulation (DIC) occurs in a variety of diseases and syndromes. Platelet count, prothrombin time, and levels of fibrinogen and D-dimer are used to determine if a patient has DIC. The tissue factor (TF)/factor (F)VIIa complex plays a central role in the activation of coagulation in sepsis. In Gram-negative sepsis, lipopolysaccharide induces TF expression in monocytes and release TF-positive extracellular vesicles (EVs). OBJECTIVE: This study determined whether EV-TF activity is associated with DIC in patients with sepsis. METHODS: We studied 2 cohorts of patients with sepsis: a cohort of sequential patients that included 143 patients without DIC and 45 patients with DIC, and a cohort of selected patients that included 39 patients without DIC and 36 patients with DIC. The first cohort had longitudinal samples taken, and the second cohort had samples taken from pre-DIC patients (who developed DIC during the study). Healthy subjects were used as controls. Plasma EV-TF activity was measured using an in-house assay.
2. Context-specific predictors of mortality and the performance of paediatric sepsis scores in Tanzanian children: a secondary analysis of a prospective cohort study.
In a prospective cohort of 755 Tanzanian children with sepsis, mortality was 20% and was independently associated with age, malnutrition, HIV status, referral status, and delayed presentation. The Lambaréné Organ Dysfunction Score had the highest discrimination and sensitivity, whereas Blantyre quick Sequential Organ Failure Assessment and Phoenix Sepsis Score had higher specificity but lower sensitivity; overall discrimination did not differ significantly.
Impact: This is an externally relevant evaluation of pediatric sepsis scores in a resource-limited setting, where validation data are scarce and disease presentation differs from high-income settings. The results support context-specific score selection and highlight modifiable delays and vulnerability factors.
Clinical Implications: LODS may be useful when high sensitivity and a high negative predictive value are priorities, whereas BqSOFA or PSS may be useful when specificity is prioritized. Local protocols should also emphasize early referral and presentation, nutritional assessment, and recognition of HIV-related risk.
Key Findings
- Among 755 children with sepsis, in-hospital mortality was 20% (148 deaths).
- Independent mortality predictors were age, malnutrition, HIV status, referral status, and delayed presentation, with p<0.001.
- LODS had an AUC of 0.79, sensitivity of 93%, and negative predictive value of 96%; BqSOFA and PSS had higher specificity but lower sensitivity.
Methodological Strengths
- Prospective cohort data from 755 children in a real-world resource-limited emergency department.
- Multivariable analysis of clinical and sociodemographic predictors combined with external performance assessment of three pediatric sepsis scores.
Limitations
- The study was a secondary analysis from a single hospital, which may limit generalizability to other regions and health systems.
- Scores showed only moderate discrimination, and the observational design cannot determine whether score-guided care improves outcomes.
Future Directions: Further multicenter validation should assess locally calibrated thresholds, serial score measurement, integration with malnutrition and HIV status, and the effect of score-guided triage on time to treatment and mortality.
INTRODUCTION: Sepsis is a significant cause of global child mortality, disproportionately affecting resource-limited settings (RLS). Although clinical scores have been proposed in RLS, few have been externally validated. This study aimed to identify risk factors for mortality among Tanzanian children with sepsis and test three paediatric clinical scores in an RLS. METHODS: We conducted a secondary analysis of a prospective cohort study of 755 children (28 days to 14 years) with sepsis in the Emergency Department at Muhimbili National Hospital, Tanzania (July 2022-November 2024). Demographic, clinical and outcome data were collected. We performed multivariable logistic regression to identify independent predictors of in-hospital mortality. We then tested three clinical scores, Lambaréné Organ Dysfunction Score (LODS), Blantyre quick Sequential Organ Failure Assessment (BqSOFA) and Phoenix Sepsis Score (PSS), using sensitivity, specificity and area under the receiver operating characteristic curve (AUC). RESULTS: In-hospital mortality was 20% (n=148); independent predictors included age, malnutrition, HIV status, referral status and delayed presentation (p<0.001).
3. Prognostic value of von Willebrand factor and ADAMTS-13 in patients with sepsis-induced coagulopathy.
In a prospective cohort of 240 ICU patients with sepsis, 63.3% met criteria for sepsis-induced coagulopathy. VWF/ADAMTS-13 activity and antigen ratios were not independent diagnostic markers after accounting for variables included in the coagulopathy score, but higher ratios were independently associated with 28-day mortality among patients with established coagulopathy.
Impact: The study separates prognostic from diagnostic utility, showing that endothelial-coagulation imbalance may identify mortality risk after sepsis-induced coagulopathy is established rather than diagnose the syndrome itself. This distinction is clinically important for avoiding inappropriate biomarker-driven diagnosis.
Clinical Implications: VWF/ADAMTS-13 ratios may help refine risk assessment in patients with established sepsis-induced coagulopathy, but their modest discrimination does not support routine standalone use. They should be interpreted alongside clinical severity, coagulation scores, and organ dysfunction.
Key Findings
- Among 240 ICU patients with sepsis, 152 (63.3%) met criteria for sepsis-induced coagulopathy.
- Patients with sepsis-induced coagulopathy had lower ADAMTS-13 activity and higher VWF/ADAMTS-13 ratios than patients without the coagulopathy.
- VWF/ADAMTS-13 ratios were not independent diagnostic markers but were independently associated with 28-day mortality, with AUCs of 0.66 and 0.65.
Methodological Strengths
- Prospective consecutive enrollment of ICU patients meeting Sepsis-3 criteria.
- Use of multivariable regression, receiver operating characteristic analysis, and survival analysis with separate evaluation of diagnostic and prognostic associations.
Limitations
- The cohort was from a single hospital and included only 240 patients, limiting external generalizability.
- The biomarkers showed modest discrimination and were measured early at a single initial time point rather than serially.
Future Directions: Larger multicenter studies should evaluate serial VWF and ADAMTS-13 measurements, determine clinically useful thresholds, and test whether biomarker-guided interventions can reduce mortality in sepsis-induced coagulopathy.
BACKGROUND: The von Willebrand factor (VWF)- a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13 (ADAMTS-13) axis may contribute to microvascular thrombosis and poor outcomes in sepsis-induced coagulopathy (SIC). OBJECTIVES: The aim of this study was to characterize the VWF-ADAMTS-13 axis in SIC and evaluate whether VWF/ADAMTS-13 ratios are associated with SIC diagnosis and 28-day mortality. METHODS: In this prospective cohort study, 240 adult patients in the intensive care unit meeting Sepsis-3 criteria were consecutively enrolled at the First Hospital of Jilin University from February to October 2025. VWF antigen, factor VIII, ADAMTS-13 activity, and ADAMTS-13 antigen were measured within 24 hours of enrollment. VWF/ADAMTS-13 activity and antigen ratios were calculated. International Society on Thrombosis and Haemostasis SIC and overt disseminated intravascular coagulation scores were derived. The primary outcome was 28-day all-cause mortality. Associations were assessed using multivariable logistic regression, receiver operating characteristic curve analysis, and Kaplan-Meier survival analysis. RESULTS: Overall, 152 patients (63.3%) met SIC criteria.