Evidence map›Paper›PMID 42472813›Full record

ArticleJournal of translational medicine2026

Lyophilized platelet derived extracellular vesicles promote hemostasis and attenuate intracranial hemorrhage following traumatic brain injury.

Alpa Trivedi, Byron Miyazawa, Alexander T Fields, Michael Matthews, Lindsay Vivona, Callie Keane, Daniel Potter, Huimin Geng, Haoqian Zhang, Hiroki Taenaka and 13 more

Abstract read
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Article in Journal of translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

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0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors.

Alpa TrivediDepartment of Laboratory Medicine, University of California, San Francisco, 513 Parnassus Avenue, HSE 715, San Francisco, CA, 94143, USA.
Byron MiyazawaDepartment of Laboratory Medicine, University of California, San Francisco, 513 Parnassus Avenue, HSE 715, San Francisco, CA, 94143, USA.
Alexander T FieldsDepartment of Surgery, University of California, San Francisco, San Francisco, CA, USA.
Michael MatthewsCellphire Therapeutics, Inc, Rockville, MD, USA.
Lindsay VivonaDepartment of Laboratory Medicine, University of California, San Francisco, 513 Parnassus Avenue, HSE 715, San Francisco, CA, 94143, USA.
Callie KeaneDepartment of Laboratory Medicine, University of California, San Francisco, 513 Parnassus Avenue, HSE 715, San Francisco, CA, 94143, USA.
Daniel PotterDepartment of Laboratory Medicine, University of California, San Francisco, 513 Parnassus Avenue, HSE 715, San Francisco, CA, 94143, USA.
Huimin GengDepartment of Laboratory Medicine, University of California, San Francisco, 513 Parnassus Avenue, HSE 715, San Francisco, CA, 94143, USA.
Haoqian ZhangDepartment of Laboratory Medicine, University of California, San Francisco, 513 Parnassus Avenue, HSE 715, San Francisco, CA, 94143, USA.
Hiroki TaenakaDepartment of Anesthesia, Cardiovascular Research Institute, University of California, San Francisco, CA, USA.
Serena S KwekDivision of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA, 94143, USA.
Kimberly Herrera-RodriguezDepartment of Surgery, University of California, San Francisco, San Francisco, CA, USA.
Brenda Nunez-GarciaDepartment of Surgery, University of California, San Francisco, San Francisco, CA, USA.
Erika Marques de MenezesVitalant Research Institute, San Francisco, CA, 94118, USA.
Mark BarryDepartment of Surgery, University of California, San Francisco, San Francisco, CA, USA.
Alison NairDepartment of Pediatrics, University of California, San Francisco, San Francisco, CA, USA.
Ben KuhnCellphire Therapeutics, Inc, Rockville, MD, USA.
Philip J NorrisDepartment of Laboratory Medicine, University of California, San Francisco, 513 Parnassus Avenue, HSE 715, San Francisco, CA, 94143, USA.
Lawrence FongFred Hutchinson Cancer Center, Seattle, WA, USA.
Michael M FitzpatrickCellphire Therapeutics, Inc, Rockville, MD, USA.
Martin SchreiberDepartment of Surgery, Uniformed Services University, Bethesda, MD, USA.
Lucy Z KornblithDepartment of Surgery, University of California, San Francisco, San Francisco, CA, USA.
Shibani PatiDepartment of Laboratory Medicine, University of California, San Francisco, 513 Parnassus Avenue, HSE 715, San Francisco, CA, 94143, USA. Shibani.pati@ucsf.edu.

Funding

U.S. Department of Defense W81XWH-20-1-0216 BA190168
6 · The paper itself

Abstract

backgroundHemorrhage is the leading cause of preventable death world-wide. Traumatic brain injury (TBI) is the primary driver of mortality and morbidity among individuals aged 1-44 years worldwide, with intracranial hemorrhage (ICH) being the major contributor to acute mortality post-TBI. Based on prior studies, we hypothesized that lyophilized platelet-derived extracellular vesicles (LPEVs) would reduce ICH and preserve blood-brain barrier (BBB) integrity after TBI.

methodsLPEVs were characterized by flow cytometry, scanning electron microscopy, and Nanosight. LPEVs were evaluated in vitro in human brain endothelial cell monolayers for barrier integrity. Utilizing a murine TBI model of controlled cortical impact, LPEVs were transfused 40 min after injury. The degree of BBB permeability was quantitated by 10kD infrared-tagged dye that leakage into the brain. ICH was quantitated by RBCs using Ter-119 antibody. Murine tail snip and cremaster muscle vascular injury models and thromboelastography analysis of healthy donor or trauma patient blood were used to assess hemostatic ability of LPEVs. Proteomic content was analyzed by mass spectrometry and mRNA and miRNA content by next-generation sequencing. Light transmission aggregometry using fresh apheresis platelets or generated dysfunctional platelets supported the mechanistic pathway assessment.

resultsLPEVs were predominantly in the exosome range, expressed platelet and microvesicle markers and generated thrombin. In vitro, LPEVs attenuated thrombin-induced paracellular permeability and reduced intercellular gaps in human brain microvascular endothelial cells. In vivo, LPEVs exhibited potent hemostatic activity in a murine tail-transection and cremaster vascular injury models. Following experimental TBI in mice, acute administration of LPEVs significantly reduced ICH without impacting BBB permeability. Multi-omics analyses revealed that LPEVs retained platelet-derived hemostatic cargo, but lacked the vasculoprotective factors, typically present in intact platelets. LPEVs accelerated clot formation in blood from healthy donors, trauma patients, and dysfunctional platelet preparations. Mechanistically, LPEVs promote hemostasis in part through GPIIb/IIIa-dependent platelet aggregation.

conclusionsThese data demonstrate the therapeutic and hemostatic efficacy of LPEVs in reducing ICH following TBI without affecting BBB permeability or neuroinflammation. The multi-omics and GPIIB/IIIA driven data can potentially explain the decoupled effects of LPEVs on hemostasis and vascular permeability in our experimental TBI model.

Indexed as

Blood PlateletsBrain Injuries, TraumaticExtracellular VesiclesHemostasisIntracranial HemorrhagesAnimalsBlood-Brain BarrierEndothelial CellsFreeze DryingHumansMaleMiceMice, Inbred C57BLBlood brain barrierDysfunctional plateletsExosomesGPIIb/IIIaLight transmission aggregometryThrombinTraumatic brain injury

Identifiers

PMID42472813

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Registered trials

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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.