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Medwave 2015;15(Suppl 3):e6330 doi: 10.5867/medwave.2015.6330

�Es efectivo el �cido tranex�mico en la hemorragia digestiva alta aguda?

Is tranexamic acid effective for acute upper gastrointestinal bleeding?

Sebasti�n Flores, Carolina Avil�s, Gabriel Rada

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Abstract

Upper gastrointestinal bleeding constitutes a medical-surgical emergency given its important associated morbidity and mortality. The antifibrinolytic tranexamic acid might help stopping bleeding, but controversy remains about its role in this setting. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified five systematic reviews including eight randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded tranexamic acid probably decreases rebleeding and mortality, without increasing thromboembolic adverse effects in patients with upper gastrointestinal bleeding.

Problem

Acute upper gastrointestinal bleeding is a common condition in emergency departments and critical care units. Most cases are self-limited, but there is a percentage of patients close to 30% in which bleeding persists or recurs, leading to high morbidity and mortality [1].

Tranexamic acid, an antifibrinolytic that reduces fibrin degradation assisting in the formation of blood clot, has been postulated among treatment options. This drug has proven effectiveness in trauma patients, but its role in upper gastrointestinal bleeding is not yet clearly defined.

Methods

We used Epistemonikos database, which is maintained by screening more than 30 databases, to identify systematic reviews and their included primary studies. With this information, we generated a structured summary using a pre-established format, which includes key messages, a summary of the body of evidence (presented as an evidence matrix in Epistemonikos), meta-analysis of the total of studies, a summary of findings table following the GRADE approach and a table of other considerations for decision-making.

Key messages

Tranexamic acid probably decreases bleeding and mortality from upper gastrointestinal bleeding without increasing the risk of thromboembolic side effects.
Risk/benefit and cost/benefit of use of tranexamic acid are probably favorable.
An ongoing study of high methodological quality and big sample size will provide valuable information to increase the certainty of the evidence.

About the body of evidence for this question

What is the evidence. See evidence matrix in Epistemonikos later	We found five systematic reviews [2],[3],[4],[5],[6] that consider 11 primary studies reported in 13 references [7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19], including eight randomized controlled trials [7],[8],[9],[10],[11],[13],[14],[19]. This table and the summary in general are based on the latter.
What types of patients were included	In six studies, the average age exceeded 50 years [7],[8],[9],[13],[14],[19]. The remaining two studies did not report the age of the patients [10],[11] Confirmation of gastrointestinal bleeding was performed using medical records in one study [14], through the presence of hematemesis or melena in four studies [8],[9],[10],[11], with upper gastrointestinal endoscopy in two studies [7],[19], and one study did not report this aspect [13]. Regarding severity, two studies included patients with massive gastrointestinal bleeding and unstable hemodynamics [9],[13], one study included severe upper gastrointestinal bleeding [7], and the remaining five studies did not report severity [8],[10],[11],[14],[19].
What types of interventions were included	Three studies administered tranexamic acid orally [9],[11],[14], while the other five studies used it orally or intravenously. One study used tranexamic acid for less than three days [9], two studies between 3 and 4 days [7],[14] and five studies for over 5 days to a maximum of 7 days [8],[10],[11],[13],[19]. All studies compared against placebo or standard treatment.
What types of outcomes were measured	Different systematic reviews reported meta-analysis for the following outcomes: Mortality, rebleeding, need for surgery, required transfusions, adverse events (acute myocardial infarction, pulmonary embolism, stroke, deep vein thrombosis).

Summary of findings

Information on the effects of tranexamic acid in upper gastrointestinal bleeding is based on eight randomized controlled studies involving 1701 patients [7],[8],[9],[10],[11],[12],[13],[14],[19]. All studies provided information on mortality, and seven studies provided information on risk of rebleeding [7],[8],[10],[11],13],[14],[19].

Tranexamic acid probably reduces mortality in upper gastrointestinal bleeding. The certainty of the evidence is moderate.
Tranexamic acid probably reduces rebleeding in upper gastrointestinal bleeding. The certainty of the evidence is moderate.
Tranexamic acid probably does not increase the risk of thromboembolic serious adverse effects. The certainty of the evidence is moderate.

Other considerations for decision-making

To whom this evidence does and does not apply

This evidence applies to patients presenting to emergency services with upper gastrointestinal bleeding.
Even though studies included patients older than 50 years in average, it is reasonable to extrapolate this evidence to younger patients, in whom a similar effect could be expected as there are no major morphological or physiological differences. The risk of adverse effects, if they exist, would be less in the latter since they have a lower baseline risk.
Studies included patients with severe upper gastrointestinal bleeding, but since there were no major differences with less severe bleeding, it is reasonable to extrapolate the results from this group, although the expected benefit would be lower.

About the outcomes included in this summary

We selected mortality, rebleeding and thromboembolic adverse events for inclusion in the summary of findings table, as these constitute outcomes critical for decision-making in the opinion of the authors of this summary. This coincides with the outcomes cited in systematic reviews and major guidelines.

Balance between benefits and risks, and certainty of the evidence

The risk of serious adverse events was very low in the studies evaluated in this summary, which is consistent with that observed in multiple studies in other areas [20]. Tranexamic acid may produce nausea, vomiting, anorexia, hypertension, dizziness and diarrhea in some patients.
While the certainty of the evidence is moderate, the benefits of this intervention on the main outcomes make the balance probably favorable to its use.

Resource considerations

The cost of tranexamic acid is relatively low. By contrasting it with the observed benefit makes it probably cost-effective.

Differences between this summary and other sources

The findings of our summary are consistent with the conclusion of the systematic reviews identified, although some of them present a more cautious conclusion about the certainty of the evidence.
Our conclusions differ with the main guidelines; the guideline of the American College of Gastroenterology [21] on peptic ulcer bleeding does not mention the use of tranexamic acid, and the guideline on management of non-variceal bleeding from the European Society of Gastrointestinal Endoscopy does not recommend it, because of the low certainty of the evidence [22].

Could this evidence change in the future?

The probability that future evidence change the findings of this summary is low because of the certainty of the evidence.
The evidence on the benefits of this intervention in similar pathophysiological situations has not changed with the accumulation of new evidence [20].
The certainty of the evidence will surely increase with data from the HALT-IT study, which is ongoing and expects to incorporate nearly five times more patients than all previous studies combined [23].

How we conducted this summary

Using automated and collaborative means, we compiled all the relevant evidence for the question of interest and we present it as a matrix of evidence.

Follow the link to access the interactive version: Tranexamic acid for upper gastrointestinal bleeding

Notes

The upper portion of the matrix of evidence will display a warning of “new evidence” if new systematic reviews are published after the publication of this summary. Even though the project considers the periodical update of these summaries, users are invited to comment in Medwave or to contact the authors through email if they find new evidence and the summary should be updated earlier. After creating an account in Epistemonikos, users will be able to save the matrixes and to receive automated notifications any time new evidence potentially relevant for the question appears.

The details about the methods used to produce these summaries are described here http://dx.doi.org/10.5867/medwave.2014.06.5997.

Epistemonikos foundation is a non-for-profit organization aiming to bring information closer to health decision-makers with technology. Its main development is Epistemonikos database (www.epistemonikos.org).

These summaries follow a rigorous process of internal peer review.

Conflicts of interest
The authors do not have relevant interests to declare.

Licencia Creative Commons

Esta obra de Medwave est� bajo una licencia Creative Commons Atribuci�n-NoComercial 3.0 Unported. Esta licencia permite el uso, distribuci�n y reproducci�n del art�culo en cualquier medio, siempre y cuando se otorgue el cr�dito correspondiente al autor del art�culo y al medio en que se publica, en este caso, Medwave.

Edici�n Julio 2022

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