Tranexamic acid corrects fibrinolysis in the presence of acidemia in a swine model of severe ischemic reperfusion

DeBarros, Mia; Hatch, Quinton; Porta, Christopher R.; Salgar, Shashikumar K.; Izenberg, Seth; DuBose, Joseph J.; Eckert, Matthew J.; Martin, Matthew J.

doi:10.1097/ta.0000000000000143

Cited by 11 publications

(4 citation statements)

References 28 publications

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“…16 The ability of TXA to inhibit tPA-induced fibrinolysis had been demonstrated previously in an acidotic, coagulopathic swine model. 17 They used human recombinant tPA and injected it intravenously into their hemorrhaged, acidotic swine model to induce a transient fibrinolysis. We confirmed that human tPA does induce fibrinolysis in swine plasma, but we found that swine were 30-fold less sensitive to human rtPA and porcine tPA, although it should be noted that we did not use the same brand of human rtPA as that used by DeBarros et al 17 Interestingly, human plasma was affected equally by both human and swine tPA.…”

Section: Discussionmentioning

confidence: 99%

“…17 They used human recombinant tPA and injected it intravenously into their hemorrhaged, acidotic swine model to induce a transient fibrinolysis. We confirmed that human tPA does induce fibrinolysis in swine plasma, but we found that swine were 30-fold less sensitive to human rtPA and porcine tPA, although it should be noted that we did not use the same brand of human rtPA as that used by DeBarros et al 17 Interestingly, human plasma was affected equally by both human and swine tPA. Therefore, swine show more species specificity than the human in the response to tPA-induced fibrinolysis.…”

Section: Discussionmentioning

confidence: 99%

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Double-blinded, placebo-controlled study of early tranexamic acid treatment in swine uncontrolled hemorrhage model

Sondeen

Hanson²,

Prince³

et al. 2016

Journal of Trauma and Acute Care Surgery

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Double-blinded, placebo-controlled study of early tranexamic acid treatment in swine uncontrolled hemorrhage model

Sondeen

Hanson²,

Prince³

et al. 2016

Journal of Trauma and Acute Care Surgery

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show abstract

“…Therefore, the development of effective and easy to administer therapeutic interventions targeting hyperfibrinolysis and subsequent TIC in severe trauma patients is a high priority. The Food and Drug Administration–approved antifibrinolytic tranexamic acid (TXA) is a synthetic lysine analog that inhibits plasminogen activation, thereby leading to decreased clot lysis 11,12 . Current Tactical Combat Casualty Care and Military Clinical Practice Guidelines, as well as civilian trauma centers, recommend intravenous (IV) TXA administration within 3 hours of severe traumatic injury 13,14 .…”

mentioning

confidence: 99%

“…The Food and Drug Administration-approved antifibrinolytic tranexamic acid (TXA) is a synthetic lysine analog that inhibits plasminogen activation, thereby leading to decreased clot lysis. 11,12 Current Tactical Combat Casualty Care and Military Clinical Practice Guidelines, as well as civilian trauma centers, recommend intravenous (IV) TXA administration within 3 hours of severe traumatic injury. 13,14 Its use has been shown to reduce mortality when given within these first 3 hours.…”

mentioning

confidence: 99%

Intramuscular administration of tranexamic acid in a large swine model of hemorrhage with hyperfibrinolysis

Haberkorn,

Severance,

Wetmore

et al. 2023

J Trauma Acute Care Surg

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Background Traumatic injury with subsequent hemorrhage is one of the leading causes of mortality among military personnel and civilians alike. Post traumatic hemorrhage accounts for 40-50% of deaths in severe trauma patients occurring secondary to direct vessel injury or the development of trauma induced coagulopathy (TIC). Hyperfibrinolysis plays a major role in TIC and its presence increases a patient’s risk of mortality. Early therapeutic intervention with intravenous (IV) tranexamic acid (TXA) prevents development of hyperfibrinolysis and subsequent TIC leading to decreased mortality. However, obtaining IV access in an austere environment can be challenging. In this study, we evaluated the efficacy of intramuscular (IM) versus IV TXA at preventing hyperfibrinolysis in a hemorrhaged swine. Methods Yorkshire cross swine were randomized on the day of study to receive IM or IV TXA or no treatment. Swine were sedated, intubated, and determined to be hemodynamically stable prior to experimentation. Controlled hemorrhaged was induced by the removal of 30% total blood volume. After hemorrhage, swine were treated with 1000 mg of IM or IV TXA. Control animals received no treatment. Thirty minutes post TXA treatment, fibrinolysis was induced with a 50 mg bolus of tissue plasminogen activator (tPA). Blood samples were collected to evaluate blood TXA concentrations, blood gases, blood chemistry, and fibrinolysis. Results Blood TXA concentrations were significantly different between administration routes at the early timepoints, but were equivalent by 20 minutes after injection, remaining consistently elevated for up to three hours post administration. Induction of fibrinolysis resulted in 87.18 ± 4.63% lysis in control animals, compared to swine treated with IM TXA 1.96 ± 2.66 % and 1.5 ± 0.42% lysis in the IV TXA group. Conclusion In the large swine model of hemorrhage with hyperfibrinolysis, IM TXA is bioequivalent and equally efficacious in preventing hyperfibrinolysis as IV TXA administration.

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Blood Transfusion Safety in the Operating Room

Neilsen,

Dudaryk,

Yeh

2024

Principles of Perioperative Safety and Efficiency

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Tranexamic acid corrects fibrinolysis in the presence of acidemia in a swine model of severe ischemic reperfusion

Abstract: TXA rapidly and fully reverses hyperfibrinolysis despite severe acidemia in a porcine trauma model. TXA is a promising adjunct to trauma resuscitation that is easily administered in austere or prehospital settings.

Cited by 11 publications

References 28 publications

Double-blinded, placebo-controlled study of early tranexamic acid treatment in swine uncontrolled hemorrhage model

Double-blinded, placebo-controlled study of early tranexamic acid treatment in swine uncontrolled hemorrhage model

Intramuscular administration of tranexamic acid in a large swine model of hemorrhage with hyperfibrinolysis

Blood Transfusion Safety in the Operating Room

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