Page 42 - JSOM Fall 2020

resuscitation has been completed.” This requires a clarifica- release in extremity surgery—have repeatedly found that
tion how “initial fluid resuscitation” is defined. TXA should TXA use decreases bleeding without increasing the risk of
be administered as early as possible after the injury, taking the DVT and PE. 23,85,86,142–148 Orthopedic trauma surgery studies
tactical situation and prioritization of interventions (MARCH) have also not found an increase in VTE. 5,149–151 A review of
into account. The phrase “after initial fluid resuscitation has cardiac surgery also found no increase in VTE. Some newer
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been completed” has been removed from the updated TCCC studies of use in trauma have not shown an increase rate of
Guidelines. The updated administration recommendations VTE 1,64,105,152,153 while some have noted an increase. 103,154 When
and dosing protocol eliminate the need for this decision point. given to over 10,000 patients with post-partum hemorrhage,
no increase in VTE was noted. A large meta-analysis includ-
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Should the Dose of TXA as Administered in TCCC ing 22 studies and over 49,000 patients who received TXA
Be Modified in the Presence of Ongoing Hemorrhage? for non-surgical bleeding noted no increase in venous or ar-
In the presence of ongoing hemorrhage and massive transfu- terial thrombotic events. The discussion is further compli-
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sion, the impact of both decreased renal clearance of TXA and cated by historical data showing that trauma patients have
loss of a portion of the TXA dose through blood loss must higher rates of VTE than non-trauma patients 156–158 and a
be considered. A recent paper noted that: “Scenarios involv- recent review of the Joint Trauma Registry concluding that
ing large patients requiring massive transfusion may benefit TXA may increase non-fatal VTE but “potential mortality
from a replacement strategy.” Replacement dosing schemes benefit likely outweighs the potential risks of fatal PE.” In
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159
should be identified using simulations and tested in large ani- a large meta-analysis evaluating TXA use in TBI published
mal model.” However, this paper also demonstrated that TXA in 2018, the authors noted no effect on VTE rates. In the
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levels were relatively preserved during hemorrhage, with only TAMPITI trial, active screening for VTE was completed on
a 25% decrease after one total body blood volume loss and all patients with an increase noted in the TXA group in a dose
replacement. In the WOMAN Trial, a second dose of TXA (or dependent manner. Given the time- sensitive nature of TXA
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placebo) was only given if bleeding continued after 30 min- administration and the challenges of delivering care in aus-
utes or restarted within 24 hours. The World Health Orga- tere environments, it is reasonable to anticipate that patients
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nization updated dosing recommendations for TXA based on may receive TXA who ultimately are determined not to need
this trial in 2017 and currently recommends a second dose of it. In one retrospective review of military TXA use, overuse
TXA for ongoing bleeding after 30 minutes or if bleeding re- was estimated at 6.4% and was associated with an increased
starts within 24 hours of completing the first dose. Less than risk of VTE. Two recent reviews also noted variation in the
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30% of the patients who received one dose received a second incidence of VTE after TXA administration 161,162 with one
dose and whether or not the second dose provided clinically concluding that “the application of TXA to trauma patients
significant benefit was not explored or discussed. 43 may pose a certain risk for possible thromboembolic compli-
cations.” In CRASH-3 (isolated TBI), no difference in VTE
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Based on limited available evidence and the personal experi- rate between TXA and placebo groups was noted. A large
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ence of the authors, an evidence-based recommendation for meta-analysis of the over 28,000 patients from the CRASH-2
redosing of TXA in the prehospital setting cannot be made at and WOMAN trials published in 2020 found “the risk of vas-
this time. Measuring fibrinolytic status to guide TXA dosing cular occlusive events was similar according to baseline risk
continues to be debated in the literature reported out of trauma categories.” 107
centers, but the technology required to measure fibrinolytic
status is not available in the prehospital setting. The change It is the opinion of the authors of this change that adminis-
group recommends exploration of this topic in future studies, tering a 2g initial dose of TXA in trauma will require careful
along with more investigation of the most effective serum con- attention to appropriate thromboprophylaxis and close obser-
centration required for trauma. In a Prolonged Casualty Care vation for venous thromboembolic disease.
scenario, redosing may be considered in conjunction with per-
sonal expertise or through access to remote teleconsultation. Conclusions

Can TXA Be Administered through the Same Line The conclusions of this working group include the following
as Hextend? answers to the posed questions:
Although the preferred resuscitation fluid in TCCC is – Should a TBI Indication Be Added to the TXA Recommen-
whole blood, Hextend is still, at the time of this writing, a dations in the TCCC Guidelines and the Dose Increased to
TCCC-recommended resuscitation fluid if no blood products 2 Grams?

are available and medics ask if it is possible to administer TXA Yes
in Hextend infusions. The Physicians’ Desk Reference states – Is There a Need to Reinforce the Need for Timely Admin-
that TXA “May be mixed with most solutions for infusion istration of TXA When Indicated?
such as electrolyte, carbohydrate, amino acid, and dextran Yes
solutions.” Hextend is not mentioned. Recent studies how-
ever, found that “There was no evidence of incompatibility – Is There a Need for a Second Dose of TXA to be Adminis-
between the solutions of Hextend and TXA by either visual tered as Part of TCCC, Given the Discussion of the Phar-
inspection or by digital turbidimeter.” 140,141 macokinetics of TXA Mentioned Above?
No, there is not enough evidence to support a second
dose in TCCC.
What Is the Current State of Evidence that TXA Causes
an Increase in the Risk of Deep Venous Thrombosis and – Should the Second Dose of TXA Be Administered If More
Pulmonary Embolism? Than 3 Hours Have Elapsed Since the Time of Wounding.
The studies of TXA use in elective surgery—when TXA is rou- No, there is not enough data at the present time to rec-
tinely given pre-operatively or before the time of tourniquet ommend redosing in the prehospital setting.

40 | JSOM Volume 20, Edition 3 / Fall 2020