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Should EMS administer Tranexamic Acid (TXA)?

There is much we don’t know about how TXA works and its role in reducing mortality from severe hemorrhage

Based on the TXA Drug Why article, you may understand why many trauma surgeons fail to be impressed with Tranexamic Acid (TXA) or advocate for prehospital administration.

We know that TXA appears to have an ability to reduce bleeding deaths in critically injured trauma patients in severe shock. The greatest advantage is seen when TXA is administered within the first hour (32 percent mortality reduction) and between one and three hours, mortality is reduced by 20 percent. There appears to be an increased risk of death from bleeding when TXA is given more than three hours after injury.

We do not know whether TXA has any impact on mortality when damage-control resuscitation and massive transfusion protocols are employed (both MATTERS and MATTERS-II raised questions about the role of blood component products). We do not know the optimal dosing and timing of TXA for trauma (look at the wide variations in dosing TXA for other conditions) or whether other antifibinolytic agents would work equally well or better.

We do not know if TXA is associated with seizures in trauma patients, particularly with TBI (traumatic brain injury). TXA doses in patients undergoing cardiac surgery, although two to 10 times trauma doses, have increased incidence of neurological complications. The FDA added a warning to TXA labeling in 2012, “Convulsions have been reported in association with tranexamic acid treatment.”

Finally, we have no proof for why TXA works. In theory, TXA prevents clot breakdown and improves coagulation. Few studies have done laboratory analysis for fibrinolysis in patients given TXA. In spring 2015, several papers were published calling for more rational use of TXA and other blood products given the widespread availability of whole blood fibrinolysis tests such as thromboelastography (TEG: Haemonetics, Braintree, MA) and thromboelastometry (ROTEM: Tem International, Munich, Germany). These tests allow carefully targeted and therefore safer selection and administration of blood products and antifibinolytics. They are widely used in trauma and cardiac surgery today.

Inhibition of plasmin by TXA results in activation of monocytes, neutrophils, platelets and endothelial cell as well as release of cytokine and lipid mediators and induction of proinflammatory gene effects. One of the lingering questions raised by critical thinkers reading TXA studies is whether mortality benefits come from antifibrinolytic actions of TXA or perhaps modulating the immune mediated inflammatory effects of trauma. Measuring fibrinolytic activity in trauma patients would help us lean in one or the other direction. Until then, how TXA works is purely theoretical speculation.

Aside from EMS systems in the U.S. with TXA protocols, TXA has been in use for several years in systems in the U.K., Norway, Israel and France. Many augment TXA with blood products such as freeze-dried plasma and packed red blood cells. The U.S. Department of Defense recently approved TXA for prehospital use. As additional studies are completed, the prehospital role of TXA will be better understood.

References

1. Lexicomp: Wolters Kluwer Health, Hudson, Ohio (accessed June, 2015).

2. Albany Medical Center Pharmacy, Albany, New York.

3. Napolitano LM, Cohen MJ, Cotton BA, Schreiber MA, Moore EE. Tranexamic acid in trauma: How should we use it? J Trauma Acute Care Surg. 2013; 74:1575-1586.

4. Ausset S, Glassberg E. Nadler R, Sunde G, Cap AP, Hoffmann C, Plang S, Sailliol A. Tranexamic acid as a part of remote damage-control resuscitation in the prehospital setting: A critical appraisal of the medical literature and available alternatives. J Trauma Acute Care Surg. 2015; 78:S70-S75.

5. Morrison JJ, Dubose JJ, Rasmussen TE, Midwinter MJ. Military application of tranexamic acid in trauma emergency resuscitation (MATTERS) study. Arch Surg. 2012; 147: 113-119.

6. Moore EE, Moore HB, Gonzalez E, Chapman MP, Hansen KC, Sauaia A, Silliman CC, Banerjee A. Postinjury dibrinolysis shutdown: rationale for selective tranexamic acid. J Trauma Acute Care Surg. 2015; 78:S65-S69.

EMS1.com columnist Mike McEvoy, is the EMS coordinator for Saratoga County and the EMS director on the Board of the New York State Association of Fire Chiefs. Mike is the Fire-EMS technical editor for Fire Engineering magazine and has authored numerous publications including the book, “Straight Talk About Stress for Emergency Responders.”
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