Observational studyCritical care (London, England)2021
Coagulation phenotypes in sepsis and effects of recombinant human thrombomodulin: an analysis of three multicentre observational studies.
Observational study in Critical care (London, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
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Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 107 citations in OpenAlex.
- Exploring alternative approaches to precision medicine through genomics and artificial intelligence - a systematic review.Frontiers in medicine · 2023Pooled it
- Systems Bioengineering of Septic Shock Metabolism: Citrulline, β-Hydroxybutyrate and Plasma Biomarker-Based Phenotyping.Biomolecules · 2026Review
- The Acute Respiratory Distress Syndrome (ARDS): epidemiology, etiology, molecular mechanisms, diagnosis and therapeutic strategies.Molecular biomedicine · 2026Review
- Deep eutectic solvents@enteric technology for orally delivering anticoagulant macromolecule drug.Acta pharmaceutica Sinica. B · 2026Article
- Association of Shenfu injection with reduced 28-day mortality in critically ill patients with sepsis: a retrospective propensity score-matched cohort study.BMC infectious diseases · 2026Article
- Delayed anticoagulation is associated with lower mortality in sepsis-induced coagulopathy: a large-scale, propensity-score-matched cohort study from MIMIC-IV.International journal of surgery (London, England) · 2026Article
- Clinical subphenotypes of sepsis based on mixed continuous and categorical data and differences in treatment effects: a cluster analysis of multicenter observational studies.Critical care (London, England) · 2026Observational
- Correlation between sub-phenotypes of coagulopathy and prognosis in sepsis patients in ICU using longitudinal group trajectory modeling: a retrospective analysis.European journal of medical research · 2026Article
- Artificial Intelligence- and Machine Learning-Assisted Subphenotyping for Personalized Immunotherapy in Sepsis.Journal of personalized medicine · 2026Review
- Identification and Characterization of Sepsis Phenotypes in an Indian Cohort.Critical care research and practice · 2026Article
- Thrombomodulin: a potential biomarker for sepsis-associated acute kidney injury resulting from bacterial infections.Frontiers in cellular and infection microbiology · 2026Observational
- The immunology of sepsis: translating new insights into clinical practice.Nature reviews. Nephrology · 2026Review
- Hyper-inflammation and immunosuppression: redefining sepsis therapy using modern approaches.Frontiers in pharmacology · 2026Review
- Longitudinal sepsis-induced coagulopathy score trajectories and mortality in relation to early prophylactic heparin: a multicentre cohort study.Frontiers in cellular and infection microbiology · 2026Article
- Revisiting the Concept of DIC: A Phenotype-guided Framework for Modern Hemostatic Medicine.Juntendo medical journal · 2026Review
- Normal initial lactate level in sepsis patients: is lactate still useful for prognosis prediction?World journal of emergency medicine · 2026Article
- Stratified assessment of platelets in sepsis: from dynamic counts to functional phenotypes.Frontiers in immunology · 2026Review
- [Inflammatory phenotypes in sepsis and the role of vitamin C on the corresponding phenotypes].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Article
- Whole transcriptome analysis reveals T cell signaling activation in septic patients with thrombocytopenia.Scientific reports · 2025Article
- Clinical value of combined detection of procalcitonin, D-dimer and fibrinogen in the evaluation of children with sepsis.Pakistan journal of medical sciences · 2025Article
Corrections and comments
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Authors and funding
8 authors at 7 institutions in 1 country.
Funding
Abstract
backgroundA recent randomised trial showed that recombinant thrombomodulin did not benefit patients who had sepsis with coagulopathy and organ dysfunction. Several recent studies suggested presence of clinical phenotypes in patients with sepsis and heterogenous treatment effects across different sepsis phenotypes. We examined the latent phenotypes of sepsis with coagulopathy and the associations between thrombomodulin treatment and the 28-day and in-hospital mortality for each phenotype.
methodsThis was a secondary analysis of multicentre registries containing data on patients (aged ≥ 16 years) who were admitted to intensive care units for severe sepsis or septic shock in Japan. Three multicentre registries were divided into derivation (two registries) and validation (one registry) cohorts. Phenotypes were derived using k-means with coagulation markers, platelet counts, prothrombin time/international normalised ratios, fibrinogen, fibrinogen/fibrin-degradation-products (FDP), D-dimer, and antithrombin activities. Associations between thrombomodulin treatment and survival outcomes (28-day and in-hospital mortality) were assessed in the derived clusters using a generalised estimating equation.
resultsFour sepsis phenotypes were derived from 3694 patients in the derivation cohort. Cluster dA (n = 323) had severe coagulopathy with high FDP and D-dimer levels, severe organ dysfunction, and high mortality. Cluster dB had severe disease with moderate coagulopathy. Clusters dC and dD had moderate and mild disease with and without coagulopathy, respectively. Thrombomodulin was associated with a lower 28-day (adjusted risk difference [RD]: - 17.8% [95% CI - 28.7 to - 6.9%]) and in-hospital (adjusted RD: - 17.7% [95% CI - 27.6 to - 7.8%]) mortality only in cluster dA. Sepsis phenotypes were similar in the validation cohort, and thrombomodulin treatment was also associated with lower 28-day (RD: - 24.9% [95% CI - 49.1 to - 0.7%]) and in-hospital mortality (RD: - 30.9% [95% CI - 55.3 to - 6.6%]).
conclusionsWe identified four coagulation marker-based sepsis phenotypes. The treatment effects of thrombomodulin varied across sepsis phenotypes. This finding will facilitate future trials of thrombomodulin, in which a sepsis phenotype with high FDP and D-dimer can be targeted.
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