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• W2952938981 endingPage "1644" @default.
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• W2952938981 abstract "BackgroundTrauma‐associated hemorrhage and coagulopathy remain leading causes of mortality. Such coagulopathy often leads to a hyperfibrinolytic phenotype where hemostatic clots become unstable because of upregulated tissue plasminogen activator (tPA) activity. Tranexamic acid (TXA), a synthetic inhibitor of tPA, has emerged as a promising drug to mitigate fibrinolysis. TXA is US Food and Drug Administration‐approved for treating heavy menstrual and postpartum bleeding, and has shown promise in trauma treatment. However, emerging reports also implicate TXA for off‐target systemic coagulopathy, thromboembolic complications, and neuropathy.ObjectiveWe hypothesized that targeted delivery of TXA to traumatic injury site can enable its clot‐stabilizing action site‐selectively, to improve hemostasis and survival while avoiding off‐target effects. To test this, we used liposomes as a model delivery vehicle, decorated their surface with a fibrinogen‐mimetic peptide for anchorage to active platelets within trauma‐associated clots, and encapsulated TXA within them.MethodsThe TXA‐loaded trauma‐targeted nanovesicles (T‐tNVs) were evaluated in vitro in rat blood, and then in vivo in a liver trauma model in rats. TXA‐loaded control (untargeted) nanovesicles (TNVs), free TXA, or saline were studied as comparison groups.ResultsOur studies show that in vitro, the T‐tNVs could resist lysis in tPA‐spiked rat blood. In vivo, T‐tNVs maintained systemic safety, significantly reduced blood loss and improved survival in the rat liver hemorrhage model. Postmortem evaluation of excised tissue from euthanized rats confirmed systemic safety and trauma‐targeted activity of the T‐tNVs.ConclusionOverall, the studies establish the potential of targeted TXA delivery for safe injury site‐selective enhancement and stabilization of hemostatic clots to improve survival in trauma." @default.
• W2952938981 created "2019-06-27" @default.
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• W2952938981 date "2019-10-01" @default.
• W2952938981 modified "2023-10-15" @default.
• W2952938981 title "Trauma‐targeted delivery of tranexamic acid improves hemostasis and survival in rat liver hemorrhage model" @default.
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• W2952938981 doi "https://doi.org/10.1111/jth.14552" @default.
• W2952938981 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31220416" @default.
• W2952938981 hasPublicationYear "2019" @default.
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