Professional Documents
Culture Documents
Tranexamic Acid (TXA)
for Major Bleeding
Daniel L Arellano, PhD(c), RN, ACNP‐BC, CCRN, CEN, CFRN, EMT‐P
University of Texas MD Anderson Cancer Center
Department of Critical Care
Houston, Texas
Disclosures
▪ Conflict of Interest: None
What is TXA?
▪ Antifibrinolytic
▪ A synthetic analog of the amino acid
lysine.
▪ Works by reducing conversion of
plasminogen to plasmin, preventing
fibrin degradation.
▪ Clots remain viable and stop
hemorrhage.
What is TXA?
▪ 8X the antifibrinolytic activity of an
aminocaproic acid (Amicar)
▪ included in the WHO list of essential
medicines.
▪ inexpensive and effective
What is TXA?
CRASH‐2
▪ Randomized, placebo‐
controlled, double‐blinded
study
▪ N= 20,200 patients.
▪ 274 clinical centers
participating
▪ 40 countries throughout
the world, mainly Western
Europe, Sub‐Saharan Africa
and Western India.
CRASH‐2
▪ The risk of death due to bleeding was significantly reduced
– (4.9% in the TXA group vs. 5.7% in the placebo group).
▪ There was no significant increase in mortality due to vascular
occlusive events (e.g., PE, deep vein thrombosis [DVT], stroke or MI)
▪ All‐cause mortality was significantly reduced in the TXA treatment
arm
– (14.5%) vs. the placebo (16%).
CRASH‐2
▪ In bleeding patients, a significant reduction in mortality resulted
from TXA administration within 1 hour of injury.
▪ This benefit continued up to 3 hours post‐injury, but after 3 hours,
TXA administration was found to be harmful.
MATTERs Study
▪ Retrospective
observational trial
▪ United States military
hospital based in
Afghanistan
▪ Two year time frame
▪ N=896; 293 received TXA
MATTERs Study
▪ TXA group had a lower 48‐hour mortality than the no‐TXA group
– (11.3% vs. 18.9%, respectively; p = 0.004)
▪ Lower unadjusted mortality than the no‐TXA group
– (17.4% vs 23.9%, respectively; p = 0.03).
▪ The benefit was greatest in those who received a massive transfusion
▪ TXA group showed improvement in coagulopathy
▪ TXA group had a higher occurrence of DVT and PE
▪ TXA was more severely injured; increased injury burden has been
associated with more thrombotic events
Pediatrics PED‐TRAX
▪ TXA is safe to give in pediatric
patients.
▪ TXA was independently associated
with decreased mortality among all
766 patients studied who were 18
years or younger (p = 0.03).
▪ There was no significant difference
in thromboembolic complications or
other cardiovascular events reported
in this retrospective study.
▪ Side effect of TXA is seizures. seen
mainly in the pediatric cardiac
surgery population
Other Trials/Applications
▪ Postpartum hemorrhage
▪ Tooth extraction in hemophilia patients
– Original FDA Approval
▪ Orthopedic surgery
▪ Cardiothoracic Surgery
▪ GI Bleeding
▪ Epistaxis (topical)
▪ Lung Bleeding (inhaled)
TXA Tips
▪ Definitive hemorrhage control and rapid transport to a trauma center is the key to
survival in the bleeding patient
▪ TXA administration should never delay transport.
▪ Clear hand‐off given by EMS providers specifically noting that the TXA bolus has
been given
▪ Prehospital TXA should be administered only to patients with non‐compressible
bleeding.
▪ Patients receiving prehospital TXA should be preferentially transported to a Level I
or II trauma center if available.
▪ Cost: $27.60 to $50.40 per 10 mL vial (1,000 mg/10 mL).
▪ Current off‐label dosing recommendations are 10 mg/kg up to 1,000 mg over 15
minutes within 3 hours of bleeding, followed by a 1 mg/kg/hr infusion for 8 hours
(based on CRASH‐2 data)
Arguments Against TXA
▪ Side Effects: ▪ Timing of TXA Administration
– Headache (50.4 – 60.4%)
– Backache (20.7 – 31.4%)
– Nasal sinus problem (25.4%) ▪ Study Methodologies
– Abdominal pain (12 – 19.8%) Retrospective
– Diarrhea (12.2%)
– Fatigue (5.2%)
– Anemia (5.6%)
▪ Rare side effects include:
– Pulmonary embolism
– Deep vein thrombosis
– Anaphylaxis
– Visual disturbances
Thoughts…
▪ “In the bleeding patient, hemorrhage control and appropriate
resuscitation remain the priority. Prehospital TXA use should never
supersede field bleeding control techniques, rapid transport to a
trauma center, or the administration of blood or plasma.”
▪ “All available data drawn from studies that utilize TXA for EMS show
significant benefit in all‐cause mortality. This is a drug that belongs in
the EMS community. TXA saves lives and needs to be given as soon
as possible after severe traumatic hemorrhagic injury.”
References
▪ Fischer, P. E., Bulger, E. M., Perina, D. G., Delbridge, T. R., Gestring, M. L., Fallat, M. E., ... & Zietlow, S. P. (2016). Guidance
document for the prehospital use of tranexamic acid in injured patients. Prehospital Emergency Care, 20(5), 557‐559.
▪ CRASH‐2 trial collaborators, Shakur H, Roberts I, Bautista R, Caballero J, Coats T, Dewan Y, El‐Sayed H, Gogichaishvili T, Gupta S,
et al. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant
haemorrhage (CRASH‐2): a randomised, placebocontrolled trial. Lancet. 2010;376:23.
▪ 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
▪ 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;74:1575‐86.
▪ Carr, MJ , Mell, HK, Weingart, SD , DiCorpo, JE & Merlin, MA. (2018). An Interdisciplinary Literature Review of Prehospital Use of
Tranexamic Acid (TXA) in Major Bleeding. Journal of Emergency Medical Services. Available at:
https://www.jems.com/articles/print/volume‐43/issue‐1/features/an‐interdisciplinary‐literature‐review‐of‐prehospital‐use‐of‐
tranexamic‐acid‐txa‐in‐major‐bleeding.html
▪ Lysteda (tranexamic acid) Package Insert" (PDF). accessdata.FDA.gov. Archived (PDF) from the original on 4 March 2016
Questions?
Daniel L Arellano, PhD(c), RN, ACNP‐BC, CCRN, CEN, CFRN, EMT‐P
University of Texas MD Anderson Cancer Center
Department of Critical Care
Houston, Texas
▪ DLArellano@MDAnderson.org