Early tranexamic acid administration ameliorates the endotheliopathy of trauma and shock in an in vitro model

Diebel, Lawrence N.; Martin, Jonathan V.; Liberati, David M.

doi:10.1097/ta.0000000000001445

Cited by 47 publications

(54 citation statements)

References 40 publications

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“…CRASH-3 trial showed that the mortality benefits after adjustment were most pronounced when TXA was given < 3 h in mild-moderate Glasgow Coma Scale (GCS) score, however, mortality seemed to be the same in severe GCS score [13]. Which is in accordance with the abovementioned study that the early administration is better [18]. In a small RCT by Yutthakasemsunt et al, no mortality benefit was demonstrated in a mean time from injury of 7.1 h [11].…”

Section: Discussionsupporting

confidence: 80%

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Tranexamic acid is associated with reduced mortality, hemorrhagic expansion, and vascular occlusive events in traumatic brain injury – meta-analysis of randomized controlled trials

July

Pranata

2020

BMC Neurol

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Background: This systematic review and meta-analysis aimed to synthesize the latest evidence on the efficacy and safety of tranexamic acid (TXA) on traumatic brain injury (TBI). Methods:We performed a systematic literature search on topics that compared intravenous TXA to placebo in patients with TBI up until January 2020 from several electronic databases.Results: There were 30.522 patients from 7 studies. Meta-analysis showed that TXA was associated with reduced mortality (RR 0.92 [0.88, 0.97], p = 0.002; I 2 : 0%) and hemorrhagic expansion (RR 0.79 [0.64, 0.97], p = 0.03; I 2 : 0%). Both TXA and control group has a similar need for neurosurgical intervention (p = 0.87) and unfavourable Glasgow Outcome Scale (GOS) (p = 0.59). The rate for vascular occlusive events (p = 0.09), and its deep vein thrombosis subgroup (p = 0.23), pulmonary embolism subgroup (p = 1), stroke subgroup (p = 0.38), and myocardial infarction subgroup (p = 0.15) were similar in both groups. Subgroup analysis on RCTs with low risk of bias showed that TXA was associated with reduced mortality and hemorrhagic expansion. TXA was associated with reduced vascular occlusive events (RR 0.85 [0.73, 0.99], p = 0.04; I 2 : 4%). GRADE was performed for the RCT with low risk of bias subgroup, it showed a high certainty of evidence for lower mortality, less hemorrhage expansion, and similar need for neurosurgical intervention in TXA group compared to placebo group.Conclusion: TXA was associated with reduced mortality and hemorrhagic expansion but similar need for neurosurgical intervention and unfavorable GOS. Vascular occlusive events were slightly lower in TXA group on subgroup analysis of RCTs with low risk of bias.

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Section: Discussionsupporting

confidence: 80%

“…It prevent plasmin activation, reduces fibrinolysis, and stabilizes clot, without enhancing new clot formation [17]. Early TXA administration < 60 min has been shown to attenuate endothelial apoptosis and necrosis [18]. TXA has been shown to modulate pulmonary inflammation in trauma-induced acute lung injury [19].…”

Section: Discussionmentioning

confidence: 99%

Tranexamic acid is associated with reduced mortality, hemorrhagic expansion, and vascular occlusive events in traumatic brain injury – meta-analysis of randomized controlled trials

July

Pranata

2020

BMC Neurol

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“…aprotinin) on the inflammatory response . A recent publication also reported reduced lung barrier permeability by TXA in a rat model of polytrauma , while TXA was also recently reported to reduce ‘endothelialopathy’ of trauma and shock in an in vitro model . Hence it is reasonable to suggest that the blockade of plasmin generation by TXA in coagulopathic trauma patients, or indeed in other conditions associated with severe bleeding, may also have unintended consequences on outcome ; such effects could even be beneficial and may have contributed to the beneficial effects reported with TXA administration in the CRASH‐2 trial.…”

Section: The Influence Of the Plasminogen Activating System On The Immentioning

confidence: 98%

Fibrinolysis: from blood to the brain

Medcalf

2017

Journal of Thrombosis and Haemostasis

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We all know about classical fibrinolysis, how plasminogen activation by either tissue-type plasminogen activator (t-PA) or urokinase-type plasminogen activator (u-PA) promotes fibrin breakdown, and how this process was harnessed for the therapeutic removal of blood clots. While this is still perfectly true and still applicable to thromboembolic conditions today, another dimension to this system came to light over two decades ago that implicated the plasminogen activating system in a context far removed from the dissolution of blood clots. This unsuspected area related to brain biology where t-PA was linked to a plethora of activities in the CNS, some of which do not necessarily require plasmin generation. Indeed, t-PA either directly or via plasmin, has been shown to not only have key roles in modulating astrocytes, neurons, microglia, and pericytes, but also to have profound effects in a number of CNS conditions, including ischaemic stroke, severe traumatic brain injury and also in neurodegenerative disorders. While compelling insights have been obtained from various animal models, the clinical relevance of aberrant expression of these components in the CNS, although strongly implied, are only just emerging. This review will cover these areas and will also discuss how the use of thrombolytic agents and anti-fibrinolytic drugs may potentially have impacts outside of their clinical intention, particularly in the CNS.

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“…Tranexamic acid has protective effects on the endothelium and shows beneficial modulation of inflammation and other responses following ischaemia and reperfusion. 1,6 However, at times, reduced inflammatory response might be deleterious. This perspective has been suggested by the Glue Grant investigations, 7 which used a dataset obtained from 22 US trauma centres and examined the genomics of injury in a 12-year trial.…”

Section: Tranexamic Acid: Is It About Time?mentioning

confidence: 99%

“…One RCT showed lower survival with early enhanced feeding after hypophosphataemia 2 and in some studies enhanced feeding compromised recovery, 3 but most often the dosing, timing, and route of nutrition did not seem to affect hard clinical endpoints. [4][5][6] Such negative Nutrition in the ICU: sometimes route does matter and WOMAN trials. 2,3 Patients with severe brain injury or multi-organ trauma are more likely to present with shutdown of fibrinolysis than with massive bleeding.…”

Section: Tranexamic Acid: Is It About Time?mentioning

confidence: 99%

Tranexamic acid: is it about time?

Dries

2018

The Lancet

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Early tranexamic acid administration ameliorates the endotheliopathy of trauma and shock in an in vitro model

Abstract: Antifibrinolytic and other protective effects of TXA administration on endothelial injury are time-dependent. This study supports the concept that the clinical efficacy of TXA administration requires "early administration."

Cited by 47 publications

References 40 publications

Tranexamic acid is associated with reduced mortality, hemorrhagic expansion, and vascular occlusive events in traumatic brain injury – meta-analysis of randomized controlled trials

Tranexamic acid is associated with reduced mortality, hemorrhagic expansion, and vascular occlusive events in traumatic brain injury – meta-analysis of randomized controlled trials

Fibrinolysis: from blood to the brain

Tranexamic acid: is it about time?

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