ArticleBlood2021
Anticoagulation targeting membrane-bound anionic phospholipids improves outcomes of traumatic brain injury in mice.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Extracellular vesicles as bioactive nanotherapeutics: An emerging paradigm for regenerative medicine.Theranostics · 2022Pooled it
- Hyperadhesive von Willebrand Factor Contributes to Pathogenesis of Preeclampsia.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Early identification of vascular cognitive impairment from a multimodal perspective: a combined diagnosis from targeted cognitive assessments, imaging biomarkers, and molecular fluid biomarkers to ecological behavioral characteristics.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Longitudinal changes in coagulation-fibrinolysis in patients with traumatic brain injury within seven days after injury.iScience · 2026Article
- Blood-brain barrier breakdown in traumatic brain injury: current insights and future directions.Cancer gene therapy · 2026Review
- A commentary on "The role of coagulopathy and subdural hematoma thickness at admission in predicting the prognoses of patients with severe traumatic brain injury: a multicenter retrospective cohort study from China".International journal of surgery (London, England) · 2026Article
- Reticuline modulates astrocyte and microglial responses to enhance prognosis after traumatic brain injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Injury induced endotheliopathy: overview, diagnosis, and management.Current opinion in critical care · 2025Review
- Metabolically aberrant extracellular mitochondria induce oxidative endotheliopathy in traumatic brain injury.Blood advances · 2025Article
- Ghrelin may protect against vascular endothelial injury in Acute traumatic coagulopathy by mediating the RhoA/ROCK/MLC2 pathway.Journal of thrombosis and thrombolysis · 2025Article
- Role of damage-associated molecular patterns in the pathogenesis and therapeutics of traumatic brain injury.Burns & trauma · 2025Review
- Article
- Yin-Yang: two sides of extracellular vesicles in inflammatory diseases.Journal of nanobiotechnology · 2024Review
- Extracellular vesicles in disorders of hemostasis following traumatic brain injury.Frontiers in neurology · 2024Review
- Roles and therapeutic potential of different extracellular vesicle subtypes on traumatic brain injury.Cell communication and signaling : CCS · 2023Review
- Extracellular vesicles, hyperadhesive von willebrand factor, and outcomes of gastric cancer: a clinical observational study.Medical oncology (Northwood, London, England) · 2023Observational
- Antibody-basedNeurophotonics · 2022Article
- Cell-Derived Exosomes as Therapeutic Strategies and Exosome-Derived microRNAs as Biomarkers for Traumatic Brain Injury.Journal of clinical medicine · 2022Review
- Brain-Derived Extracellular Vesicles Induce Vasoconstriction and Reduce Cerebral Blood Flow in Mice.Journal of neurotrauma · 2022Article
- Development of an automated machine learning-based prediction model and interactive tool for blood transfusion requirements in patients with severe traumatic brain injury.Frontiers in neurologyArticle
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
Severe traumatic brain injury (TBI) often causes an acute systemic hypercoagulable state that rapidly develops into consumptive coagulopathy. We have recently demonstrated that TBI-induced coagulopathy (TBI-IC) is initiated and disseminated by brain-derived extracellular vesicles (BDEVs) and propagated by extracellular vesicles (EVs) from endothelial cells and platelets. Here, we present results from a study designed to test the hypothesis that anticoagulation targeting anionic phospholipid-expressing EVs prevents TBI-IC and improves the outcomes of mice subjected to severe TBI. We evaluated the effects of a fusion protein (ANV-6L15) for improving the outcomes of TBI in mouse models combined with in vitro experiments. ANV-6L15 combines the phosphatidylserine (PS)-binding annexin V (ANV) with a peptide anticoagulant modified to preferentially target extrinsic coagulation. We found that ANV-6L15 reduced intracranial hematoma by 70.2%, improved neurological function, and reduced death by 56.8% in mice subjected to fluid percussion injury at 1.9 atm. It protected the TBI mice by preventing vascular leakage, tissue edema, and the TBI-induced hypercoagulable state. We further showed that the extrinsic tenase complex was formed on the surfaces of circulating EVs, with the highest level found on BDEVs. The phospholipidomic analysis detected the highest levels of PS on BDEVs, as compared with EVs from endothelial cells and platelets (79.1, 15.2, and 3.5 nM/mg of protein, respectively). These findings demonstrate that TBI-IC results from a trauma-induced hypercoagulable state and may be treated by anticoagulation targeting on the anionic phospholipid-expressing membrane of EVs from the brain and other cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.